加拿大渥太华大学Jean-Claude Béïque研究小组取得一项新突破。他们的研究开发出了通过促进血清素释放的非线性反复抑制。相关论文于2025年4月2日发表在《自然—神经科学》杂志上。

研究人员利用侧链的输入来研究小鼠DRN的加工特征，揭示了5-HT1A受体介导的5-HT神经元之间的循环连接，反驳了经典的自抑制理论。细胞电生理学和基因编码的5-HT传感器成像显示，这些反复出现的抑制连接跨越中缝，是缓慢的、随机的、强促进的和门控的尖峰输出。这些特征共同向该网络传递了高度非线性动力学，产生了激励驱动的抑制和赢者通吃的计算。在体内光遗传激活侧向缰状核输入DRN，在这些计算被预测会引发的频率下，暂时破坏听觉条件反射任务中奖励条件反应的表达。总之，这些数据确定了一个核心计算的支持下，一个意想不到的缓慢血清素能复发抑制网络。

研究人员表示，中叶背核（DRN）中的5-羟色胺（5-HT）神经元接受一系列远程输入，但该核中局部电路组织和潜在计算的指导原则在很大程度上是未知的。

附：英文原文

Title: Nonlinear recurrent inhibition through facilitating serotonin release in the raphe

Author: Lynn, Michael B., Geddes, Sean D., Chahrour, Mohamad, Maill, Sbastien, Caya-Bissonnette, La, Harkin, Emerson, Harvey-Girard, rik, Haj-Dahmane, Samir, Naud, Richard, Bque, Jean-Claude

Issue&Volume: 2025-04-02

Abstract: Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) receive a constellation of long-range inputs, yet guiding principles of local circuit organization and underlying computations in this nucleus are largely unknown. Using inputs from the lateral habenula to interrogate the processing features of the mouse DRN, we uncovered 5-HT1A receptor-mediated recurrent connections between 5-HT neurons, refuting classical theories of autoinhibition. Cellular electrophysiology and imaging of a genetically encoded 5-HT sensor revealed that these recurrent inhibitory connections spanned the raphe, were slow, stochastic, strongly facilitating and gated spike output. These features collectively conveyed highly nonlinear dynamics to this network, generating excitation-driven inhibition and winner-take-all computations. In vivo optogenetic activation of lateral habenula inputs to DRN, at frequencies where these computations are predicted to ignite, transiently disrupted expression of a reward-conditioned response in an auditory conditioning task. Together, these data identify a core computation supported by an unsuspected slow serotonergic recurrent inhibitory network.

DOI: 10.1038/s41593-025-01912-7

Source: https://www.nature.com/articles/s41593-025-01912-7