Serotonin suppresses slow oscillations by activating somatostatin interneurons via the 5-HT 2A receptor

Serotonin (5-HT) affects multiple physiological processes in the brain and is involved in a number of psychiatric disorders. 5-HT axons reach all cortical areas; however, the precise mechanism by which 5-HT modulates cortical network activity is not yet fully understood. We investigated the effects of 5-HT on slow oscillations (SO), a synchronized cortical network activity universally present across species. SO are observed during slow-wave sleep and anesthesia and are considered the default cortical activity pattern. Combining opto- and pharmacogenetic manipulations with electrophysiological recordings, we discovered that 5-HT inhibits SO within the entorhinal cortex (EC) by activating somatostatin-expressing (Som) interneurons via the 5-HT receptor (5-HTR). This receptor is involved in the etiology of different psychiatric disorders and mediates the psychological effects of many psychoactive serotonergic drugs, suggesting that 5-HT targeting of Som interneurons may play an important role in these processes.