Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex

Roberto de Filippo; Benjamin R Rost; Alexander Stumpf; Claire Cooper; John J Tukker; Christoph Harms; Prateep Beed; Dietmar Schmitz

doi:10.7554/eLife.66960

Somatostatin interneurons activated by 5-HT_2A receptor suppress slow oscillations in medial entorhinal cortex

Elife. 2021 Mar 31:10:e66960. doi: 10.7554/eLife.66960.

Authors

Roberto de Filippo^{1

2}, Benjamin R Rost³, Alexander Stumpf¹, Claire Cooper¹, John J Tukker^{1

3}, Christoph Harms^{4

5

6}, Prateep Beed^#¹, Dietmar Schmitz^#^{1

2

3

6}

Affiliations

¹ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany.
² Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Cluster of Excellence NeuroCure, Berlin, Germany.
³ German Centre for Neurodegenerative Diseases (DZNE), Berlin, Germany.
⁴ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Experimental Neurology, Berlin, Germany.
⁵ 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.
⁶ Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Einstein Center for Neurosciences Berlin, Berlin, Germany.

^# Contributed equally.

Abstract

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_2AR) play an important role in the suppression of SOs. Since 5-HT_2AR 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.

Keywords: MDMA; fenfluramine; mouse; neuroscience; serotonin; slow oscillations; somatostatin interneurons.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Entorhinal Cortex / physiology*
Interneurons / physiology*
Mice
Receptor, Serotonin, 5-HT2A / metabolism*
Serotonin / metabolism*

Substances

Receptor, Serotonin, 5-HT2A
Serotonin

Abstract

Publication types

MeSH terms

Substances

Grants and funding