美国宾夕法尼亚大学Alex Proekt、Joseph Cichon团队取得一项新突破。他们的研究发现了氯胺酮（KET）会触发新皮层兴奋性神经元活动的转换。2022年11月24日，国际学术期刊《自然-神经科学》发表了这一成果。

研究人员在小鼠中发现KET导致自发活跃的神经元受到抑制，而先前沉默的神经元变得自发激活。这种转换发生在所有皮质层和不同的皮质区域，由KET的全身和皮质应用诱导，并通过抑制小白蛋白和生长抑素中间神经元活性以及抑制NMDA受体和HCN通道产生。

综合来说，该研究结果揭示了两个基本上不重叠的皮质神经元群体：一个参与清醒，另一个导致KET诱导的大脑状态产生，这可能为理解大脑如何与周围环境脱节同时保持内部主观体验奠定基础。

据了解，大脑可以暂时与环境断开连接，同时保持活跃的、内部生成体验。这种所谓的“解离状态”可能发生在病理条件下，并在迷幻药或麻醉剂氯胺酮的影响下发生。但对产生解离状态的细胞和电路机制仍然知之甚少。

附：英文原文

Title: Ketamine triggers a switch in excitatory neuronal activity across neocortex

Author: Cichon, Joseph, Wasilczuk, Andrzej Z., Looger, Loren L., Contreras, Diego, Kelz, Max B., Proekt, Alex

Issue&Volume: 2022-11-24

Abstract: The brain can become transiently disconnected from the environment while maintaining vivid, internally generated experiences. This so-called ‘dissociated state’ can occur in pathological conditions and under the influence of psychedelics or the anesthetic ketamine (KET). The cellular and circuit mechanisms producing the dissociative state remain poorly understood. We show in mice that KET causes spontaneously active neurons to become suppressed while previously silent neurons become spontaneously activated. This switch occurs in all cortical layers and different cortical regions, is induced by both systemic and cortical application of KET and is mediated by suppression of parvalbumin and somatostatin interneuron activity and inhibition of NMDA receptors and HCN channels. Combined, our results reveal two largely non-overlapping cortical neuronal populations—one engaged in wakefulness, the other contributing to the KET-induced brain state—and may lay the foundation for understanding how the brain might become disconnected from the surrounding environment while maintaining internal subjective experiences.

DOI: 10.1038/s41593-022-01203-5

Source: https://www.nature.com/articles/s41593-022-01203-5