牛津大学Stephanie J. Cragg研究小组近日取得一项新成果。经过不懈努力，他们报道了胆碱能中间神经元对纹状体多巴胺输出的轴突抑制。2025年3月13日出版的《自然—神经科学》发表了这项成果。

在这里，研究团队发现纹状体胆碱能中间神经元（ChIs）和单峰多巴胺轴突上的尼古丁受体（nAChRs）中断了这种关系。在nAChRs介导的去极化后，随后的去极化事件的多巴胺释放被抑制了约100ms。这种抑制不是由于多巴胺或乙酰胆碱的消耗，而是由于nAChRs介导的去极化后多巴胺轴突的有限再激活，并且在背侧纹状体比腹侧纹状体更突出。在体内，nAChRs主要抑制多巴胺的释放，因为nAChRs在背纹状体中的拮抗作用提高了多巴胺传感器GRABDA2m的光纤光度法检测到的多巴胺，并促进了条件位置偏好。他们的研究结果表明，通过nAChRs作用的ChIs短暂地限制了多巴胺神经元后续动作电位的多巴胺轴突的再激活，因此根据ChIs活性产生了多巴胺释放的动态逆标。

据悉，轴突去极化是躯体动作电位触发轴突神经递质释放的必要条件。

附：英文原文

Title: An axonal brake on striatal dopamine output by cholinergic interneurons

Author: Zhang, Yan-Feng, Luan, Pengwei, Qiao, Qinbo, He, Yiran, Zatka-Haas, Peter, Zhang, Guofeng, Lin, Michael Z., Lak, Armin, Jing, Miao, Mann, Edward O., Cragg, Stephanie J.

Issue&Volume: 2025-03-13

Abstract: Depolarization of axons is necessary for somatic action potentials to trigger axonal neurotransmitter release. Here we show that striatal cholinergic interneurons (ChIs) and nicotinic receptors (nAChRs) on mouse dopamine axons interrupt this relationship. After nAChR-mediated depolarization, dopamine release by subsequent depolarization events was suppressed for ~100ms. This suppression was not due to depletion of dopamine or acetylcholine, but to a limited reactivation of dopamine axons after nAChR-mediated depolarization, and is more prominent in dorsal than in ventral striatum. In vivo, nAChRs predominantly depressed dopamine release, as nAChR antagonism in dorsal striatum elevated dopamine detected with optic-fiber photometry of dopamine sensor GRABDA2m and promoted conditioned place preference. Our findings reveal that ChIs acting via nAChRs transiently limit the reactivation of dopamine axons for subsequent action potentials in dopamine neurons and therefore generate a dynamic inverse scaling of dopamine release according to ChI activity.

DOI: 10.1038/s41593-025-01906-5

Source: https://www.nature.com/articles/s41593-025-01906-5