2026年8月26日，美国华盛顿大学Michael R. Bruchas等科学家在《自然》发表研究，揭示了内源性大麻素通过逆行增益控制促进奖赏参与的机制。

神经调节信号传导有望作为增益控制的神经机制，通过动态塑造兴奋性和抑制性快速神经传递，发挥调节神经元活动的关键调控作用。内源性大麻素信号系统是哺乳动物大脑中表达最广泛的神经调节系统，已在体外和离体实验中被证明通过逆行突触前作用来过滤兴奋性和抑制性输入。然而，内源性大麻素是否在自由活动的哺乳动物中发挥逆行增益控制作用以最终促进动机行为，此前尚未得到证实。在此，研究人员利用一系列体内生理学、成像、遗传学和基于机器学习的方法，揭示了一个基本作用：内源性大麻素的动态释放通过一个在遗传和解剖学上界定的丘脑纹状体环路，在奖赏寻求过程中控制行为参与。

附：英文原文

Title: Endocannabinoids facilitate reward engagement through retrograde gain control

Author: Marcus, David J., English, Anthony E., Chun, Gunn, Seth, Emmaline F., Oommen, Rachel, Hwang, Sabrina, Wells, Bailey A., Piantadosi, Sean C., Suko, Azra, Kenmochi, Sayaka J., Parasnis, Anupritaa A., Ancell, Ethan, Li, Yulong, Zweifel, Larry S., Land, Benjamin B., Stella, Nephi, Bruchas, Michael R.

Issue&Volume: 2026-08-26

Abstract: Neuromodulatory signalling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signalling system, the most widely expressed neuromodulatory system in the mammalian brain, has been demonstrated to filter excitatory and inhibitory inputs through retrograde, presynaptic action in vitro and ex vivo. However, whether eCBs exert retrograde gain control to ultimately facilitate motivated behaviours in freely moving mammals has not been established. Here, using a suite of in vivo physiological, imaging, genetic and machine learning-based approaches, we uncover a fundamental role for the dynamic release of eCBs in controlling behavioural engagement during reward seeking through a genetically and anatomically defined thalamostriatal circuit.

DOI: 10.1038/s41586-026-10967-w

Source: https://www.nature.com/articles/s41586-026-10967-w