Dataset Information

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

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.

SUBMITTER: de Filippo R

PROVIDER: S-EPMC8016478 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Somatostatin interneurons activated by 5-HT<sub>2A</sub> receptor suppress slow oscillations in medial entorhinal cortex.

de Filippo Roberto R Rost Benjamin R BR Stumpf Alexander A Cooper Claire C Tukker John J JJ Harms Christoph C Beed Prateep P Schmitz Dietmar D

eLife 20210331

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. ...[more]

PMID: 33789079

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Project description:Experimental and theoretical studies demonstrate that neuronal gamma oscillations crucially depend on interneurons, but current models do not consider the diversity of known interneuron subtypes. Moreover, in CA1 of the hippocampus, experimental evidence indicates the presence of multiple gamma oscillators, two of which may be coordinated by differing interneuron populations. In this article, we show that models of networks with competing interneuron populations with different postsynaptic effects are sufficient to generate, within CA1, distinct oscillatory regimes. We find that strong mutual inhibition between the interneuron populations permits distinct fast and slow gamma states, whereas weak mutual inhibition generates mixed gamma states. We develop idealized firing rate models to illuminate dynamic properties of these competitive gamma networks, and reinforce these concepts with basic spiking models. The models make several explicit predictions about gamma oscillators in CA1. Specifically, interneurons of different subtype phase-lock to different gamma states, and one population of interneurons is silenced and the other active during fast and slow gamma events. Finally, mutual inhibition between interneuron populations is necessary to generate distinct gamma states. Previous experimental studies indicate that fast and slow gamma oscillations reflect different information processing modes, although it is unclear whether these rhythms are intrinsic or imposed. The models outlined demonstrate that basic architectures can locally generate these oscillations, as well as capture other features of fast and slow gamma, including theta-phase preference and spontaneous transitions between gamma states. These models may extend to describe general dynamics in networks with diverse interneuron populations.NEW & NOTEWORTHY The oscillatory coordination of neural signals is crucial to healthy brain function. We have developed an idealized neuronal model that generates distinct fast and slow gamma oscillations, a known feature of the rodent hippocampus. Our work provides a mechanism of this phenomenon, as well as a theoretical framework for future experiments concerning hippocampal gamma. It moreover offers a tractable model of competitive gamma oscillations that is generalizable across the nervous system.

Dataset Information

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

Publications

Somatostatin interneurons activated by 5-HT<sub>2A</sub> receptor suppress slow oscillations in medial entorhinal cortex.

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