Summary: Researchers have identified a region of the brain responsible for driving action and another that suppresses action. The study reports that impulsive behaviors can be triggered or suppressed by activating these areas.
Source: Champalimaud Center for the Unknown
This is the final race. Eight athletes are lined up on the track, their feet firmly wedged against the starting blocks. They hear the countdown: “On your marks!”, “Get ready,” then, a fraction of a second before the shot, a runner leaps forward, disqualifying himself from the competition. It’s at times like these that an often overlooked aspect of behavior—the suppression of action—painfully comes to light.
A study published today in the journal Nature find out how the brain keeps us from jumping the gun.
“We discovered a brain area responsible for driving action and another for suppressing that drive. We could also trigger impulsive behavior by manipulating neurons in these areas,” said the lead author of the study, Joe Paton, director of the Champalimaud Neuroscience program in Portugal.
Solve a puzzle
Paton’s team set out to tackle a puzzle that stemmed in part from Parkinson’s disease and Huntington’s disease. These conditions manifest as movement disorders with broadly opposing symptoms. While Huntington’s patients suffer from uncontrolled and involuntary movements, Parkinson’s patients find it difficult to initiate action. Curiously, both conditions stem from a malfunction of the same region of the brain: the basal ganglia. How can the same structure support contradictory functions?
According to Paton, a valuable clue has emerged from previous studies, which have identified two major circuits in the basal ganglia: the direct and indirect pathways. It is believed that while the activity of the direct pathway promotes movement, the indirect pathway suppresses it. However, the precise way in which this interaction is achieved was largely unknown.
A timing task with a twist
Paton took an original approach to the problem. While previous studies investigated the basal ganglia during movement, Paton’s team instead focused on actively suppressing action.
The team designed a task where the mice had to determine whether an interval between two tones was longer or shorter than 1.5 seconds. If it was shorter, a reward would be provided on the left side of the box, and if it was longer, it would be available on the right.
“The key was that the mouse had to stay perfectly still in the period between the two tones,” said Bruno Cruz, a PhD student in the lab. “So even if the animal was certain the 1.5 second mark had passed, it had to suppress the urge to move until the second tone sounded, and only then go for the reward.”
The researchers tracked neural activity in both pathways as the mouse performed the task. As in previous studies, activity levels were similar when the mouse was moving. However, things changed during the action-removal period.
“Interestingly, unlike the coactivation that we and others have observed during movement, the patterns of activity between the two pathways were strikingly different during the action suppression period. The activity of the indirect pathway was higher overall and it continuously increased while the mouse waited for the second tone,” Cruz said.
According to the authors, this observation suggests that the indirect pathway flexibly supports the animal’s behavioral goals. “Over time, the mouse becomes more confident that it is in a ‘long interval’ trial. And so his urge to move becomes more and more difficult to contain. It’s likely that this continued increase in activity reflects that internal struggle,” Cruz explained.
Inspired by this idea, Cruz tested the inhibition effect of the indirect pathway. This manipulation caused the mice to behave impulsively more often, greatly increasing the number of trials where they rushed to the reward harbor prematurely. Through this innovative approach, the team effectively discovered an “impulsivity switch”.
“This finding has broad implications,” Paton said. “In addition to the obvious relevance for Parkinson’s disease and Huntington’s disease, it also offers a unique opportunity to study impulse control conditions, such as addiction and obsessive-compulsive disorder.”
In search of motivation to act
The team has identified a region of the brain that actively suppresses the will to act, but where does this drive come from? Since the direct route is supposed to promote action, the immediate suspect was the direct route from the same region. However, the mouse’s behavior was largely unaffected when the researchers inhibited it.
“We knew that the mice felt a strong urge to act because suppressing the suppression promoted impulsive-like action. But it wasn’t immediately clear where the site promoting the action might be. To answer this question, we decided to turn to computer modeling,” Paton recalled.
“Mathematical models are extremely useful for making sense of complex systems, like this one,” added Gonçalo Guiomar, a PhD student in the lab.
“We took accumulated knowledge about the basal ganglia, formulated it mathematically and tested how the system processes information. We then combined the model’s prediction with evidence from previous studies and identified a promising new candidate: the dorsomedial striatum. »
The team’s assumption was correct. Inhibition of forward pathway neurons in this new region was sufficient to alter mouse behavior. “The two regions we recorded from are located in a part of the basal ganglia called the striatum. The first domain is in charge of so-called “low-level” motor-sensory functions and the second is dedicated to “high-level” functions such as decision-making,” explains Guiomar.
From action to temptation and beyond
The authors argue that their results are contrary to the general perception of basal ganglia function, which is more centralized, and that their model offers a new perspective on basal ganglia function.
“Our study indicates that there are potentially multiple neural circuits in the brain that are constantly competing for which action to perform next. movement, but it goes even further,” Paton said.
“Neuroscience observations are at the heart of many machine learning and AI techniques. The idea that decision-making can occur through the interaction of many parallel circuits within a single system could prove useful for designing new types of intelligent systems,” he added.
Finally, Paton suggests that perhaps one of the most unique aspects of the study is its ability to access inner cognitive experiences.
“Impulsivity, temptation… These internal processes are some of the most fascinating things the brain does, because they reflect our inner life. But they’re also the hardest to study, because they don’t have many outward signs that we can measure.
“Setting up this new method was challenging, but we now have a powerful tool to study internal mechanisms, such as those involved in resisting and succumbing to temptation,” Paton concluded.
About this neuroscience research news
Original research: Access closed.
“Action suppression reveals parallel control of the adversary via striatal circuitsby Joseph Paton et al. Nature
Action suppression reveals parallel control of the adversary via striatal circuits
The direct and indirect basal ganglia pathways are classically thought to promote and suppress action, respectively. However, the observed co-activation of direct and indirect striatal middle spiny neurons (dMSN and iMSN, respectively) challenged this view.
Here, we study these circuits in mice performing an interval categorization task that requires a series of self-initiated and signaled actions and, importantly, an extended period of dynamic action suppression.
Although movement produced the co-activation of iMSNs and dMSNs in the dorsolateral sensorimotor striatum (DLS), fiber photometry and photo-identified electrophysiological recordings revealed signatures of functional opposition between the two pathways during movement. deletion of the action.
Notably, optogenetic inhibition showed that DLS circuitry was largely engaged in suppressing – not promoting – action. Specifically, iMSNs on a given hemisphere were dynamically engaged to suppress tempting contralateral action.
To understand how such region-specific circuit function arose, we constructed a reinforcement learning computational model that replicated key features of behavior, neural activity, and optogenetic inhibition.
The model predicted that parallel striatal circuits outside the DLS learned action-promoting functions, generating the temptation to act. Consistent with this, optogenetic inhibition experiments revealed that dMSNs in the dorsomedial associative striatum, unlike those in the DLS, promote contralateral actions.
These data highlight how adversarial interactions between multiple circuit- and region-specific basal ganglia processes can lead to behavioral control and establish a critical role for the sensorimotor indirect pathway in the proactive suppression of tempting actions.