Summary: A new study has identified a specific brain circuit that can push behavior into a compulsive “repeat mode,” forcing mice to continue digging and sniffing even when rewards are available. The circuit links the nucleus accumbens to the hypothalamus and then to the lateral habenula, a region involved in processing negative experiences.
Repeated activation of this pathway induced a negative internal state that made repetitive actions outweigh normal needs. Shutting down the relay between the hypothalamus and the habenula eliminated the compulsive behavior, offering new insight into conditions like OCD and addiction.
Key Facts:
- Repetitive Trigger: Activating the nucleus accumbens–hypothalamus–habenula circuit forces animals into repetitive actions.
- Negative State: Repeated stimulation induces a negative internal state that overrides natural motivations.
- Therapeutic Insight: Blocking the hypothalamus–habenula relay stops compulsive behavior, offering clues for OCD and addiction research.
Source: Karolinska Institute
Both animals and humans can become stuck in certain behaviours, but exactly how this is regulated in the brain has been unknown.
Now, researchers have been able to show that a specific nerve circuit in the brain can put behaviours into a kind of ‘repeat mode’, where mice continue to perform the same actions over and over again, even when there is no longer any reward.
The researchers investigated a neural circuit that runs from the nucleus accumbens, part of the brain’s reward system, to a region in the hypothalamus, which in turn is connected to the lateral habenula, an area that processes unpleasant experiences.
By activating this circuit using optogenetics, a method in which nerve cells are controlled by light, the researchers were able to induce a negative state in mice that led to repetitive behaviours such as digging and sniffing – even when food or other rewards were available.
“We have identified a brain circuit that can shift behaviour into a repetitive mode. This helps us understand how compulsive actions arise and may contribute to insights into conditions such as obsessive-compulsive disorder (OCD) and addiction,” says Konstantinos Meletis, professor at the Department of Neuroscience at Karolinska Institutet, who led the study together with Daniela Calvigioni, assistant professor at the same department.
The study shows that repeated activations of the circuit between the nucleus accumbens and the hypothalamus gradually induce a negative state that causes the mice to prioritise repetitive behaviours over natural needs. When the researchers shut down the relayed part of the circuit, from the hypothalamus to the habenula, the compulsive behaviour disappeared.
“This gives us a new understanding of how the brain can prioritise certain behaviours over others, even when they are not functional or rewarding,” says Konstantinos Meletis.
The results are based on a series of experiments in which the researchers combined genetic tools to identify and track specific nerve cells, methods for measuring brain activity, optogenetics to control nerve cell activity, and various behavioural tests. This made it possible to link compulsive-like behaviours to specific brain circuits.
Funding: The study is funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Wenner-Gren Foundations, StratNeuro, and the Swedish Brain Foundation. The researchers state that they have no conflicts of interest.
Key Questions Answered:
A: A pathway from the nucleus accumbens to the hypothalamus, relayed to the habenula, can shift behavior into repetitive patterns.
A: Mice show compulsive digging and sniffing even when rewards are available, reflecting a negative internal state.
A: Yes, inhibiting the hypothalamus–habenula relay removes the repetitive behavior.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience research news
Author: Press Office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A striosomal accumbens pathway drives stereotyped behavior through an aversive Esr1+ hypothalamic-habenula circuit” by Konstantinos Meletis et al. Science Advances
Abstract
A striosomal accumbens pathway drives stereotyped behavior through an aversive Esr1+ hypothalamic-habenula circuit
The lateral hypothalamic area (LHA) integrates external stimuli with internal states to drive the choice between competing innate or value-driven motivated behaviors.
Here, we define a striosomal Tac1+/Tshz1+/Oprm1+ neuron subtype in the nucleus accumbens (ACB) that targets Esr1+ LHA neurons that project to the lateral habenula (LHb).
Intersectional cell type–specific and input-output defined optogenetic activation of this ACB-LHA-LHb pathway can progressively induce a negative behavioral state that depends on Esr1+ LHA-LHb neural activity.
We found that either activation of the D1+ ACB-LHA projection or inhibition of LHA-LHb neurons defined by ACB inputs can drive reward-independent compulsive-like behaviors that generalize across contexts.
We found that these complex yet stereotyped behaviors compete with highly motivated states and can override the drive for natural rewards or social interactions.
Our findings reveal a discrete Tac1+ striosomal ACB projection targeting the aversive Esr1+ LHA-LHb pathway as a key circuit that promotes stereotyped and compulsive-like behaviors over goal-directed actions.
