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Scientists at the Okinawa Institute of Science and Technology (OIST) and Keio University School of Medicine conducted a study on the main source of serotonin in the brain, the dorsal raphe nucleus (DRN), using mice. They found that activating serotonin neurons in the DRN affects brain areas that influence behavior and motivation, such as the cerebral cortex and the basal ganglia. The distribution of serotonin receptors and connection patterns of DRN serotonin neurons played a significant role in the brain’s response to serotonin stimulation.

The brain’s serotonin system, which influences behavioral and cognitive functions like memory, sleep, and mood, is made up of neurons that communicate through neurotransmitters. Activating serotonin neurons in the DRN has been shown to promote adaptive behaviors associated with future rewards in mice, leading researchers to explore how serotonin activation affects different parts of the brain. High-field MRI images revealed that under anesthesia, the cerebral cortex and basal ganglia were mostly deactivated, while in awake states, these areas were significantly activated by serotonin stimulation.

The researchers used opto-functional MRI to observe the entire brain’s response to DRN serotonin activation. By employing optogenetics to selectively activate serotonin neurons with light, they were able to monitor changes in brain activity using functional MRI. The activation of the cerebral cortex and basal ganglia following DRN serotonin stimulation was crucial for understanding how serotonin affects cognitive functions and behaviors associated with rewards like food and water, leading to changes in motivation and behavior.

Dr. Hiroaki Hamada, the lead author of the study, faced challenges in combining high-field MRI and optogenetics techniques but overcame them with patience and determination. He adjusted the light intensity used to stimulate the DRNs to achieve brain responses visible in the MRI. Prof. Kenji Doya, leader of the Neural Computation Unit, highlighted the importance of understanding the molecular mechanisms behind brain-wide serotonin activation to help individuals improve their ability to adjust behavior and thinking in different situations by controlling moods.

The study’s findings shed light on how serotonin from the DRN affects the entire brain, providing insights into adaptive behaviors and cognitive processes. The activation of the cerebral cortex and basal ganglia by DRN serotonin can lead to changes in motivation and behavior, highlighting the role of serotonin in controlling moods and facilitating behavioral adjustments. Further research is needed to explore the molecular mechanisms underlying brain-wide serotonin activation and its implications for mood regulation and cognitive functions in different contexts.

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