Title image: Prof Ami Citri (Credit- Prof Mickey London)
A new study reveals how cocaine restricts a flexible repertoire of natural behaviors into a persistent, repetitive loop. Led by PhD students Ben Jerry Gonzales and Itay Shalom under the supervision of Prof Ami Citri at the Edmond and Lily Safra Center for Neural Sciences (ELSC) and the Institute of Life Sciences at the Hebrew University, the research identifies a specific brain circuit that normally manages natural mouth and face movements, but becomes disproportionately engaged under repeated cocaine exposure.Mapping Behavior with AI: The STEREO SystemThe striatum is a brain region vital for moment-to-moment action selection. When its capacity to properly guide actions breaks down, it often leads to the repetitive and maladaptive behaviors seen in various neurological and psychiatric conditions, including Tourette syndrome, Parkinson’s disease, and drug-induced movement disorders.To examine these processes in high definition, the team developed STEREO, a custom deep-learning system capable of identifying and tracking natural behaviors directly from video. This technology allowed researchers to track shifts across an entire behavioral repertoire over time, bypassing traditional, manual scoring methods.
“We wanted to capture behavior as an observer actually sees it: grooming, licking, exploring, but this was impossible to score manually,” explained Itay Shalom, co-first author. “STEREO allowed us to watch how the animals’ entire behavioral repertoire progressively narrowed until one type of action came to dominate.”
From Exploration to Compulsion
Using repeated exposure to cocaine as an experimental model for behavioral rigidity, the researchers observed a striking transformation. Exploratory behavior steadily narrowed until a single repetitive action took over. By the fifth day of exposure, mice spent more than 60% of their time licking the floor and walls of the enclosure—behaviors virtually never seen without the drug.The team mapped this change to the ventrolateral striatum (VLS), an area particularly involved in mouth and tongue movements. The VLS contains two major neural pathways—direct and indirect—that exert opposing influences over which actions are expressed:
- The Indirect Pathway: When researchers activated neurons in this pathway, cocaine-driven repetitive behavior stopped immediately, shifting behavior toward alternative actions. Suppressing this pathway produced the opposite effect, worsening behavioral rigidity.
- The Direct Pathway: Conversely, reducing direct-pathway activity weakened the drug-induced repetitive behavior. Activating it without any cocaine present was enough to induce rigid, repetitive patterns resembling those caused by the drug.
Hijacking, Not Inventing
Rather than manufacturing an entirely new behavioral program, the drug co-opts existing neural machinery.
“Cocaine does not appear to create an entirely new behavioral program,” noted Ben Jerry Gonzales, co-first author of the study. “It takes control of a circuit the brain already uses for natural actions and pushes behavior toward persistent repetition.”
Because this same circuit naturally handles context-appropriate grooming and licking, cocaine essentially hijacks a normal action-selection system.
Broader Implications for Neuroscience
These findings provide a clearer window into how repetitive motor behaviors emerge across diverse neurological and psychiatric conditions. Because different areas of the striatum govern different types of movement, the researchers propose that similar imbalances in adjacent striatal circuits may drive other forms of behavioral rigidity.Furthermore, the introduction of STEREO marks a major methodological leap forward for behavioral neuroscience, enabling researchers to analyze complex shifts in natural behavior at a scale and precision previously out of reach.
Media Contacts
Prof Ami Citri, Hebrew University of Jerusalem
Tel: +972 52-390-9320
Email: ami.citri@mail.huji.ac.il
Research Paper
Gonzales, B. J., Shalom, I., Lipton, D. M., Turm, H., Noble, J., Festuccia, M., Groysman, M., & Citri, A. (2026). Opponent ventrolateral striatal circuits regulate behavioral flexibility and rigidity. Current Biology DOI: 10.1016/j.cub.2026.08.068
Authors:
Ben J. Gonzales, Itay Shalom, David M. Lipton, Hagit Turm, Jed Noble, Massimiliano Festuccia, Maya Groysman, Ami Citri
Affiliations:
- The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem; Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
- The Alexander Silberman Institute of Life Science, Faculty of Science, The Hebrew University of Jerusalem; Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
- Program in Child and Brain Development, Canadian Institute for Advanced Research; MaRS Centre, Toronto, Ontario M5G 1M1, Canada.