美国斯坦福大学Neir Eshel研究小组开发出多巴胺释放的胆碱能调节驱动努力行为。该项研究成果发表在2026年1月28日出版的《自然》上。

努力是要付出代价的：如果有选择的话，人们倾向于避免它。

然而，在许多情况下，努力为随后的回报增加了价值。从蚂蚁到人类，个体都喜欢难以获得的奖励。即使在抵抗力差的环境中，这种反直觉的过程也可能促进寻求奖励，从而增强进化适应性。尽管它无处不在，但人们对支持这种行为效应的神经机制知之甚少。

在这里，该课题组表明，努力放大了多巴胺对其他相同奖励的反应，这种放大依赖于乙酰胆碱对多巴胺轴突的局部调节。高努力奖励引起局部伏核中间神经元快速释放乙酰胆碱。当奖赏传递时，乙酰胆碱与多巴胺轴突末端的尼古丁受体结合，增加多巴胺的释放。阻断胆碱能调节会在高努力环境中选择性地减弱多巴胺的释放，损害努力行为，同时保持低努力的奖励消费不变。这些结果与长期以来证明乙酰胆碱可以通过多巴胺轴突直接触发多巴胺释放的体外研究相一致，而体内研究未能观察到这种调节，但没有检查高强度环境。他们的发现揭示了一种机制，通过乙酰胆碱和多巴胺轴突之间依赖于上下文的局部相互作用来驱动努力行为。

附：英文原文

Title: Cholinergic modulation of dopamine release drives effortful behaviour

Author: Touponse, Gavin C., Pomrenze, Matthew B., Yassine, Teema, Denomme, Nicholas, Wang, May, Mehta, Viraj, Zhang, Zihui, Malenka, Robert C., Eshel, Neir

Issue&Volume: 2026-01-28

Abstract: Effort is costly: given a choice, we tend to avoid it1. However, in many cases, effort adds value to the ensuing rewards2. From ants3 to humans4, individuals prefer rewards that had been harder to achieve. This counterintuitive process may promote reward seeking even in resource-poor environments, thus enhancing evolutionary fitness5. Despite its ubiquity, the neural mechanisms supporting this behavioural effect are poorly understood. Here we show that effort amplifies the dopamine response to an otherwise identical reward, and this amplification depends on local modulation of dopamine axons by acetylcholine. High-effort rewards evoke rapid acetylcholine release from local interneurons in the nucleus accumbens. Acetylcholine then binds to nicotinic receptors on dopamine axon terminals to augment dopamine release when reward is delivered. Blocking the cholinergic modulation blunts dopamine release selectively in high-effort contexts, impairing effortful behaviour while leaving low-effort reward consumption intact. These results reconcile in vitro studies, which have long demonstrated that acetylcholine can trigger dopamine release directly through dopamine axons6,7,8,9,10,11, with in vivo studies that failed to observe such modulation12,13,14, but did not examine high-effort contexts. Our findings uncover a mechanism that drives effortful behaviour through context-dependent local interactions between acetylcholine and dopamine axons.

DOI: 10.1038/s41586-025-10046-6

Source: https://www.nature.com/articles/s41586-025-10046-6