Research reveals a specific brain circuit implicated in OCD
· Medical Xpressedited by Sadie Harley, reviewed by Robert Egan
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Treatment for obsessive-compulsive disorder (OCD), a mental health condition characterized by distressing, uncontrollable thoughts and repetitive behaviors, has centered on psychotherapy and medication to curb symptoms. New research identifying a previously unknown brain circuit involved in OCD could be a key step toward treatments that target specific brain regions to better control the condition.
Published in the journal Neuron and led by Joshua L. Plotkin, Ph.D., associate professor in the Department of Neurobiology and Behavior at the Renaissance School of Medicine (RSOM) at Stony Brook University, the research is based on a mouse model. Although the human brain differs considerably from a mouse's, their brains share strikingly similar structures and regional organization.
A small connection with outsized influence
The researchers used sensory stimuli to prompt mice to perform a behavior. During the experiments, Plotkin and his colleagues focused on two areas of the brain—the amygdala, which processes emotionally important experiences such as fear and anxiety, and the dorsolateral striatum (DLS), which is important for habitual and automatic behaviors.
The team discovered that the amygdala directly connects to and influences the DLS, a connection not identified in previous research. The connection originates from only a small number of amygdala neurons, making it easy to overlook.
Using new imaging tools to map brain circuits functionally at the single-synapse level, Zachary Hobel, the study's first author and a postdoctoral fellow in the Department of Neurobiology and Behavior, found that although the amygdala-DLS connection is small, it can have an outsized influence on the DLS.
Experimental measures and neuronal models confirmed that this connection both amplifies and promotes synaptic plasticity in other inputs to the DLS—inputs likely to encode sensory-evoked behaviors.
Stimulation prolongs grooming behavior
The team found that repeatedly stimulating inputs from the amygdala to the DLS amplifies sensory-evoked behaviors, an effect that persisted long after stimulation ended.
Placing a droplet of water on a mouse's nose prompted it to groom its face. When the researchers stimulated the amygdala-to-DLS circuit while the mouse experienced the water droplet, the same droplet subsequently caused it to groom for much longer, even after the sensation and brain stimulation had stopped. The mouse continued to respond more strongly to the water even after the experimental pairing ended.
Inhibiting the circuit prevents OCD-like behavior
The researchers also demonstrated that this circuit is stronger, more active and abnormally regulated in a mouse model of OCD. By chronically inhibiting the amygdala in these mice, they prevented OCD-like behavior—a key finding.
"Our study reveals a clear mechanism through which emotionally important experiences may strengthen the connection between sensory cues and actions, and this potentially helps to explain how otherwise normal behaviors can be transformed into compulsive behaviors," said Plotkin, the corresponding author and a researcher affiliated with Stony Brook's Center for Nervous System Disorders.
Treatment targets remain to be tested
Plotkin pointed out that the mice are a strong model of OCD because they respond to the same commonly used medications as people with OCD.
He cautioned that the exact neuronal connections and dysfunctions altered or corrected by OCD treatments are not fully known, and that the brain connections and processes underlying OCD are complex. However, the authors concluded that the findings provide important insights into OCD-like behaviors and identify specific brain circuit dysfunctions—advances that give researchers a new place to look for more precise OCD treatment targets.
Publication details
Zachary B. Hobel et al, A basolateral amygdala to dorsolateral striatum projection modulates stimulus-evoked motor behavior, Neuron (2026). DOI: 10.1016/j.neuron.2026.08.025
Journal information: Neuron
Key medical concepts
Obsessive-Compulsive DisorderAmygdala
Clinical categories
PsychiatryPsychology & Mental healthNeurology Provided by Stony Brook University Who's behind this story?
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