PMID- 33789079 OWN - NLM STAT- MEDLINE DCOM- 20210910 LR - 20210910 IS - 2050-084X (Electronic) IS - 2050-084X (Linking) VI - 10 DP - 2021 Mar 31 TI - Somatostatin interneurons activated by 5-HT(2A) receptor suppress slow oscillations in medial entorhinal cortex. LID - 10.7554/eLife.66960 [doi] LID - e66960 AB - 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-HT(2A) receptor (5-HT(2A)R) play an important role in the suppression of SOs. Since 5-HT(2A)R 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. CI - (c) 2021, de Filippo et al. FAU - de Filippo, Roberto AU - de Filippo R AUID- ORCID: 0000-0002-4085-9114 AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany. AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Cluster of Excellence NeuroCure, Berlin, Germany. FAU - Rost, Benjamin R AU - Rost BR AD - German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany. FAU - Stumpf, Alexander AU - Stumpf A AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany. FAU - Cooper, Claire AU - Cooper C AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany. FAU - Tukker, John J AU - Tukker JJ AUID- ORCID: 0000-0002-4394-199X AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany. AD - German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany. FAU - Harms, Christoph AU - Harms C AUID- ORCID: 0000-0002-2063-2860 AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Department of Experimental Neurology, Berlin, Germany. AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Center for Stroke Research Berlin, Berlin, Germany. AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Einstein Center for Neurosciences Berlin, Berlin, Germany. FAU - Beed, Prateep AU - Beed P AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany. FAU - Schmitz, Dietmar AU - Schmitz D AUID- ORCID: 0000-0003-2741-5241 AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany. AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Cluster of Excellence NeuroCure, Berlin, Germany. AD - German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany. AD - Charite-Universitatsmedizin Berlin, corporate member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin Institute of Health; Einstein Center for Neurosciences Berlin, Berlin, Germany. LA - eng GR - SFB1315-327654276/Bundesministerium fur Bildung und Forschung/ GR - SPP1926/Deutsche Forschungsgemeinschaft/ GR - SPP1665/Deutsche Forschungsgemeinschaft/ GR - 01GQ1420B/Deutsche Forschungsgemeinschaft/ GR - HA5741/5-1/Deutsche Forschungsgemeinschaft/ GR - TRR295/Deutsche Forschungsgemeinschaft/ GR - 01EO0801/Bundesministerium fur Bildung und Forschung/ GR - EXC-2049 - 390688087/NeuroCure Exzellenzcluster/ GR - BIH Fellowship/Charite - Universitatsmedizin Berlin/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210331 PL - England TA - Elife JT - eLife JID - 101579614 RN - 0 (Receptor, Serotonin, 5-HT2A) RN - 333DO1RDJY (Serotonin) SB - IM MH - Animals MH - Entorhinal Cortex/*physiology MH - Interneurons/*physiology MH - Mice MH - Receptor, Serotonin, 5-HT2A/*metabolism MH - Serotonin/*metabolism PMC - PMC8016478 OTO - NOTNLM OT - MDMA OT - fenfluramine OT - mouse OT - neuroscience OT - serotonin OT - slow oscillations OT - somatostatin interneurons COIS- Rd, BR, AS, CC, JT, CH, PB, DS No competing interests declared EDAT- 2021/04/01 06:00 MHDA- 2021/09/11 06:00 PMCR- 2021/03/31 CRDT- 2021/03/31 20:06 PHST- 2021/01/27 00:00 [received] PHST- 2021/03/10 00:00 [accepted] PHST- 2021/03/31 20:06 [entrez] PHST- 2021/04/01 06:00 [pubmed] PHST- 2021/09/11 06:00 [medline] PHST- 2021/03/31 00:00 [pmc-release] AID - 66960 [pii] AID - 10.7554/eLife.66960 [doi] PST - epublish SO - Elife. 2021 Mar 31;10:e66960. doi: 10.7554/eLife.66960.