Scientists have uncovered a powerful strategy that the brain uses to coordinate chemical signaling. In a new study, researchers found that in the striatum, a brain region central to learning and moving, one chemical signaling system can effectively seize control of another, promoting the coordinated release of both. Specifically, they showed that a brain chemical called “acetylcholine”, which rises and falls to signal important behavioral events, can directly trigger the release of serotonin, a neurotransmitter long linked to mood and psychiatric disorders. What’s more, the researchers showed that because of this strong link, changes in acetylcholine signaling in disease states can lead to parallel changes in serotonin levels. Given that drugs targeting the serotonin system are the first line treatment for many psychiatric conditions, such as Obsessive-Compulsive Disorder and depression, these findings offer a new perspective on the origins of chemical imbalances that underly numerous debilitating neurological and psychiatric disorders.

 

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In a new study led by Prof. Joshua Goldberg of Hebrew University and Prof. Joshua Plotkin of Stony Brook University, the team focused on a small group of brain cells in the striatum that act like conductors in an orchestra. These cells, called cholinergic interneurons, that release acetylcholine were already known to promote the release of dopamine, the brain’s reward chemical, but the researchers discovered that their reach extends much further than expected, and they can also directly trigger the release of serotonin.

Using advanced tools that allowed them to turn specific brain cells on and off with flashes of light, the team watched what happened when these conductor cells fired together. When they did, nearby serotonin fibers responded almost instantly, releasing their chemical signals into the surrounding brain tissue.

When the researchers examined brain states linked to Obsessive-Compulsive–like behaviors, they found the system running in overdrive. The cholinergic cells were overactive, driving a surge of serotonin release. Thus a mechanism that may normally help fine-tune learning and behavior appeared to become amplified beyond normal levels.

“Our findings show that the brain’s internal wiring allows one chemical system to take the wheel of another in a highly regional and specific way,” Goldberg and Plotkin explained. “In conditions like OCD, where cholinergic signaling may be dysfunctional, this normally helpful coordination may go into overdrive, which could help explain why certain behaviors become so difficult to stop.”

The study suggests that brain disorders may not simply stem from having too much or too little of one chemical. Instead, they may involve the brain’s internal coordination system being pushed into overdrive, translating increases in one chemical into pathological increases in another.

The research paper titled “Synchronous activation of striatal cholinergic interneurons induces local serotonin release” is now available in Nature Communications and can be accessed at [doi: 10.1038/s41467-026-70359-6].

Researchers:

Lior Matityahu¹, Zachary B. Hobel², Noa Berkowitz¹, Jeffrey M. Malgady², Naomi Gilin¹, Joshua L. Plotkin², Joshua A. Goldberg¹

Institutions:

1. Department of Medical Neurobiology, Institute of Medical Research Israel – Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem
2. Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University Renaissance School of Medicine, Stony Brook University

For over a century, the Hebrew University of Jerusalem has been a beacon for visionary minds who challenge convention and shape the future. Founded by luminaries like Albert Einstein, who entrusted his intellectual legacy to the university, it is dedicated to advancing knowledge, cultivating leadership, and promoting diversity. Home to over 23,000 students from 90 countries, the Hebrew University drives much of Israel’s civilian scientific research and the commercialization of technologies through Yissum, its tech transfer company. Hebrew University’s groundbreaking contributions have been recognized with major international awards, including ten Nobel Prizes, two Turing Awards, and a Fields Medal. Ranked 88th globally by the Shanghai Ranking (2025), Hebrew University marks a century of excellence in research, education, and innovation. To learn more about the university’s academic programs, research, and achievements, visit the official website at http://new.huji.ac.il/en.