Scientists have identified a powerful strategy the brain uses to coordinate its chemical signals. In a new study, researchers showed that in the striatum – a brain region central to learning and movement – one chemical signalling system can effectively take control of another, driving the coordinated release of both.
They found that a brain chemical called acetylcholine, which rises and falls to signal important behavioural events, can directly trigger the release of serotonin, a neurotransmitter long associated with mood and psychiatric disorders. Because of this tight coupling, changes in acetylcholine signalling in disease states can produce parallel shifts in serotonin levels. As drugs that act on the serotonin system are first-line treatments for many psychiatric conditions, including obsessive-compulsive disorder (OCD) and depression, these findings offer a fresh perspective on the origins of the chemical imbalances underlying numerous neurological and psychiatric disorders.
The study, led by Prof Joshua Goldberg of the Hebrew University of Jerusalem and Prof Joshua Plotkin of Stony Brook University, focused on a small population of brain cells in the striatum that behave like orchestra conductors. These cells, known as cholinergic interneurons because they release acetylcholine, were already known to promote the release of dopamine, the brain’s “reward” chemical. The new work shows that their influence is even broader: they can also directly trigger the release of serotonin.
Using advanced techniques that allowed them to switch specific brain cells on and off with flashes of light, the team observed what happened when these conductor cells fired in synchrony. When they did, nearby serotonin fibres reacted almost immediately, releasing their chemical signals into the surrounding brain tissue.
When the researchers then examined brain states linked to OCD-like behaviours, they found the system operating in overdrive. The cholinergic cells were excessively active, driving an abnormal surge in serotonin release. A mechanism that may normally help fine‑tune learning and behaviour appeared to be amplified beyond healthy 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 signalling may be dysfunctional, this normally helpful coordination may go into overdrive, which could help explain why certain behaviours become so difficult to stop.”
The study suggests that brain disorders may not simply arise from having too much or too little of a single chemical. Instead, they may reflect dysfunction in the brain’s coordination mechanisms, which translate increases in one chemical into pathological increases in another.
The research paper, titled “Synchronous activation of striatal cholinergic interneurons induces local serotonin release”, is published in Nature Communications and can be accessed via the following DOI: 10.1038/s41467-026-70359-6.
Researchers:
Lior Matityahu, Zachary B. Hobel, Noa Berkowitz, Jeffrey M. Malgady, Naomi Gilin, Joshua L. Plotkin, Joshua A. Goldberg
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