The neuromodulatory arousal system imbues the nervous system with the flexibility and robustness required to facilitate adaptive behaviour. While there are well-understood mechanisms linking dopamine, noradrenaline and acetylcholine to distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic function and cognitive capacities as diverse as reward processing, exploration, and the psychedelic experience, over 95% of the serotonin in the body is released in the gastrointestinal tract, where it controls digestive muscle contractions (peristalsis). Here, we argue that framing neural serotonin as a rostral extension of the gastrointestinal serotonergic system dissolves much of the mystery associated with the central serotonergic system. Specifically, we outline that central serotonin activity mimics the effects of a digestion/satiety circuit mediated by hypothalamic control over descending serotonergic nuclei in the brainstem. We review commonalities and differences between these two circuits, with a focus on the heterogeneous expression of different classes of serotonin receptors in the brain. Much in the way that serotonin-induced peristalsis facilitates the work of digestion, serotonergic influences over cognition can be reframed as performing the work of cognition. Extending this analogy, we argue that the central serotonergic system allows the brain to arbitrate between different cognitive modes as a function of serotonergic tone: low activity facilitates cognitive automaticity, whereas higher activity helps to identify flexible solutions to problems, particularly if and when the initial responses fail. This perspective sheds light on otherwise disparate capacities mediated by serotonin, and also helps to understand why there are such pervasive links between serotonergic pathology and the symptoms of psychiatric disorders.

中文翻译：

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通过其在胃肠道中的作用了解血清素在大脑中的作用

神经调节唤醒系统使神经系统具有促进适应行为所需的灵活性和鲁棒性。虽然有很好理解的机制将多巴胺、去甲肾上腺素和乙酰胆碱与不同的行为状态联系起来，但对于血清素来说，类似的结论还没有那么容易获得。令人着迷的是，尽管 5-羟色胺能功能和认知能力之间存在明显的联系，如奖励处理、探索和迷幻体验，但体内超过 95% 的 5-羟色胺在胃肠道中释放，它控制消化肌肉收缩（蠕动）。在这里，我们认为将神经 5-羟色胺作为胃肠道 5-羟色胺能系统的延髓延伸解开了与中枢 5-羟色胺能系统相关的大部分谜团。具体来说，我们概述了中枢血清素活性模拟了由下丘脑控制脑干中下降的血清素能核介导的消化/饱腹感回路的作用。我们回顾了这两个回路之间的共性和差异，重点关注大脑中不同类别血清素受体的异质表达。就像血清素诱导的蠕动促进消化工作一样，血清素对认知的影响可以重新定义为执行认知工作。扩展这个类比，我们认为中枢血清素系统允许大脑根据血清素基调在不同的认知模式之间进行仲裁：低活动有助于认知自动化，而高活动有助于确定问题的灵活解决方案，特别是当初始响应失败时。这一观点揭示了由 5-羟色胺介导的其他不同能力，也有助于理解为什么 5-羟色胺能病理学与精神疾病症状之间存在如此普遍的联系。