Researchers at the HUN-REN Experimental Medical Research Institute (HUN-REN KOKI) have identified an unknown area in the brainstem that plays a role in the reward system. This finding, reported in the journal Science, could open new avenues for treating anxiety, depression, and addiction.
The brain continuously assesses whether experiences are beneficial or harmful, which aids in decision-making. In dangerous situations, this process assists in escape, while helping to choose favorite coffee shops. The neural basis of this is complex, regulated by various ancient and higher brain regions.
The lateral habenula, a subcortical structure in the diencephalon, plays a key role in processing emotions and guiding motivational processes. Activation of the lateral habenula triggers negative emotions, while its overactivity can lead to anxiety or depression. Conversely, inhibition of the lateral habenula can elicit positive emotions, which may be crucial for joy and mood disorder treatment.
In the study published in Science, researchers led by Gábor Nyiri, including Krisztián Zichó, discovered another previously unknown brain area targeting the lateral habenula. This newly identified brainstem nucleus, named the subventricular tegmentum (SVTg), provides pure inhibition to the lateral habenula.
Through a series of experiments, researchers taught mice to activate their SVTg cells voluntarily by inserting their noses into a small hole. The mice showed a strong preference for this task, indicating that SVTg activation is pleasurable. This suggests that SVTg cells may play a role in seeking pleasant experiences, potentially relating to the excessive pursuit of pleasures in humans.
Furthermore, the researchers found that SVTg activity increased not only during positive experiences but also when recalling positive memories. Mice also enjoyed direct, artificial stimulation of their SVTg cells. In challenging situations, this stimulation exhibited anxiety-reducing effects, making the mice bolder in exploring unfamiliar environments.
In contrast, inhibition of the SVTg resulted in negative experiences and heightened fear, causing the mice to avoid locations where they experienced SVTg inhibition. These and other experiments confirmed that SVTg aids in experiencing positive events and motivation, while preventing excessive fear during negative experiences.
The researchers also mapped the physiological and genetic characteristics of SVTg neurons, enabling them to locate the SVTg brain area in the brainstem of macaques and humans.