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Konstantinos Meletis, professor at the department of neuroscience, Karolinska Institutet. Photo: Andreas Andersson
Both animals and humans can get stuck in certain behaviors, but exactly how this is regulated in the brain has been unknown. Now scientists have been able to show that a specific neural circuit in the brain can put behaviors into a kind of “repetition mode”, where mice continue to perform the same actions over and over again, even when there is no longer a reward.
The researchers have examined a neural circuit that runs from the nucleus accumbens, part of the brain’s reward system, to a region in the hypothalamus that is in turn connected to the lateral habenula, an area that processes unpleasant experiences. By activating this circuit using optogenetics, a method where neurons are controlled with light, the researchers were able to induce a negative state in mice that led to repetitive behaviors such as digging and sniffing – even when food or other rewards were available.
– We have identified a brain circuit that can shift behavior into a repetitive mode. It helps us understand how compulsive actions arise and can 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 lecturer at the same department.
Prioritizes repetitive behaviors
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 prioritize repetitive behaviors over natural needs. When the researchers shut down the relayed part of the circuit, from the hypothalamus to the habenula, the compulsive behavior disappeared.
– This gives us a new understanding of how the brain can prioritize certain behaviors over others, even when they are not functional or rewarding, says Konstantinos Meletis.
The results are based on a series of experiments where the researchers combined genetic tools to identify and follow specific nerve cells, methods to measure brain activity, optogenetics to control nerve cell activity and various behavioral tests. It made it possible to link compulsive-like behaviors to specific brain circuits.
The study is funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Wenner-Gren Foundations, StratNeuro and the Brain Foundation. The researchers state that they have no conflicts of interest.
