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
bioRxiv Preprint Server May 26, 2020 preprint DOI: 10.1101/2020.05.26.113373 via bioRxiv
Summary
The study found that serotonin (5-HT) can inhibit slow oscillations (SOs) in the entorhinal cortex of anesthetized mice, particularly through the activation of somatostatin-expressing interneurons via the 5-HT2A receptor. This suggests a significant role for these interneurons in modulating cortical activity patterns influenced by serotonergic drugs, which may relate to various psychiatric disorders.
Study at a glance
| Population | anesthetized mice |
|---|---|
| Key finding | Serotonin inhibits slow oscillations in the entorhinal cortex of anesthetized mice through the activation of somatostatin-expressing interneurons via the 5-HT2A receptor. |
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-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.