March 23, 2026 – In a new study led by Prof. Joshua Goldberg of the Hebrew University of Jerusalem (HU) 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 [obsessive compulsive disorder], 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 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 here.
Researchers:
Lior Matityahu1, Zachary B. Hobel2, Noa Berkowitz1, Jeffrey M. Malgady2, Naomi Gilin1, Joshua L. Plotkin2, Joshua A. Goldberg1
Institutions:
- Department of Medical Neurobiology, Institute of Medical Research Israel – Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem
- Department of Neurobiology and Behavior, Center for Nervous System Disorders, Stony Brook University Renaissance School of Medicine, Stony Brook University
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