Μake us preferred on Google Scientists at the Hebrew University of Jerusalem have pinpointed a brain circuit that usually helps animals behave flexibly but that cocaine turns into a driver of rigid, repetitive behavior. The study, published in Current Biology, found that tipping the balance between two competing neural pathways can either lock behavior into repetition or quickly break the cycle and bring back a wider range of actions. The results shed new light on the brain processes behind compulsive and stereotyped behavior.
The research was led by PhD students Ben Jerry Gonzales and Itay Shalom, under the supervision of Prof. Ami Citri of the Edmond and Lily Safra Center for Brain Sciences (ELSC) and the university’s Institute of Life Sciences. It shows how cocaine can shrink a varied set of natural behaviors down to a single, persistent pattern. The team traced this effect to a circuit that normally helps select everyday mouth and face movements but becomes overly active as behavior narrows with repeated cocaine use.
This circuit sits in the striatum, a part of the brain that decides from moment to moment which action to carry out. When this selection process breaks down, it is linked to repetitive, rigid, and harmful behaviors found in several neurological and psychiatric conditions, such as Tourette syndrome, Parkinson’s disease, and movement disorders caused by drugs.
Watching Behavior Shrink Over Time
To study these changes closely, the researchers built STEREO, a deep-learning system that recognizes and tracks natural behaviors straight from video footage. Instead of manually labeling one action at a time, the team could follow how an animal’s full range of behaviors changed over days.
“We wanted to capture behavior as an observer actually sees it: grooming, licking, exploring, but this was impossible to score manually,” said Shalom. “STEREO allowed us to track the entire behavioral repertoire as it progressively narrowed until one type of action came to dominate.”
The researchers gave mice repeated doses of cocaine as a model of behavioral rigidity and saw a dramatic change. The animals’ varied, exploratory behavior slowly gave way to constant repetition. By the fifth day, the mice were spending more than 60% of their time licking the floor and walls of their enclosure, something they rarely did without the drug. This showed how a normally diverse set of actions can collapse into one fixed pattern.
Two Pathways Pulling in Opposite Directions
The team linked this shift to the ventrolateral striatum (VLS), a section of the striatum that mainly controls mouth and tongue movements. The VLS contains two major neural pathways, called the direct and indirect pathways, which seem to push in opposite directions when it comes to deciding which actions take place.
Activating neurons in the indirect pathway instantly stopped the cocaine-driven repetition, and the mice switched to other behaviors. As soon as the stimulation ended, the repetitive behavior quickly returned. Silencing the same pathway had the reverse effect, making it harder for the mice to switch activities and causing longer stretches of repetition.
The direct pathway worked the other way around. Turning down its activity reduced the drug-induced repetition, while switching it on in mice that had not received cocaine was enough on its own to trigger rigid, repetitive actions similar to those caused by the drug.
“Cocaine does not appear to create an entirely new behavioral program,” said Gonzales.
“It takes control of a circuit the brain already uses for natural actions and pushes behavior toward persistent repetition.”
What It Could Mean Beyond Cocaine
A key point is that this same circuit also produces normal grooming and licking when the situation calls for it. This suggests cocaine does not activate a special circuit for abnormal behavior but instead takes over a normal system the brain uses to choose actions.
The results could help scientists understand how repetitive movements develop in various neurological and psychiatric conditions. Since different parts of the striatum control different kinds of movement, the researchers suggest that similar imbalances in other striatal circuits might play a role in other types of behavioral rigidity.
The study also presents STEREO as a valuable new tool for behavioral neuroscience. Because it can automatically recognize actions in raw video, it may let researchers study complex changes in natural behavior on a scale and with a level of detail that manual observation cannot easily match.
Source: Medical Xpress
