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5-HT 受体激活的生长抑素中间神经元抑制内嗅皮层中的慢波振荡。

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

机构信息

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Neuroscience Research Center, Berlin, Germany.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Cluster of Excellence NeuroCure, Berlin, Germany.

出版信息

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

DOI:10.7554/eLife.66960
PMID:33789079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8016478/
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 receptor (5-HTR) play an important role in the suppression of SOs. Since 5-HTR 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.

摘要

血清素（5-HT）是哺乳动物大脑中主要的神经调质之一，已被证明在多种生理过程中发挥作用。然而，5-HT 调节皮质网络活动的机制尚不完全清楚。我们研究了 5-HT 对慢波（SOs）的影响，SOs 是普遍存在于各种物种中的同步皮质网络活动。SOs 在麻醉期间观察到，被认为是皮质活动的默认模式。我们发现，（±）3,4-亚甲基二氧甲基苯丙胺（MDMA）和芬氟拉明，两种强效 5-HT 释放剂，在麻醉小鼠的内嗅皮质（EC）中抑制 SOs。通过光遗传学和药理学操纵以及体外电生理记录的结合，我们发现，5-HT 受体（5-HTR）激活的生长抑素表达（Sst）中间神经元在抑制 SOs 中发挥重要作用。由于 5-HTR 信号参与了不同精神疾病的病因，并介导了许多致幻性血清素能药物的心理效应，我们提出，新发现的 Sst 中间神经元和 5-HT 之间的联系将有助于我们理解这些复杂的课题。

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