Using mice, scientists at the Okinawa Institute of Science and Technology (OIST) and their collaborators at Keio University School of Medicine have studied the main source of serotonin in the brain: the dorsal raphe nucleus (DRN). Studying for the first time how activation of the brain’s “serotonin center” affects awake animals, they discovered that DRN serotonin activates areas of the brain that affect behavior and motivation. The results show that DRN serotonin stimulation causes activation of the cerebral cortex and basal ganglia, areas of the brain involved in many cognitive functions.
Furthermore, the brain’s response to serotonin stimulation is strongly related to the distribution of serotonin receptors (serotonin-activated proteins) and the connection patterns of DRN serotonin neurons. “We clearly see in the high-field MRI images which areas of the brain are activated and deactivated during the awake state and under anesthesia when we activate serotonin neurons in the DRN,” said lead author Dr. Hiroaki Hamada. “A previous study showed that the cerebral cortex and basal ganglia were largely deactivated under anesthesia, which we also observed, but in the awake state these areas are significantly activated.”
Our brains are made up of tens of billions of nerve cells called neurons. These cells communicate with each other through biomolecules called neurotransmitters. Serotonin, a type of neurotransmitter, is produced by serotonin neurons in our brain and influences many of our cognitive and behavioral functions, such as memory, sleep, and mood.
“Learning about the brain’s serotonin system can help us understand how we adapt our behaviors and how mood therapy medications work. But it was difficult to study how DRN serotonin affects the entire brain. First, because “Electrical stimulation of the DRN can also activate neurons that do not use serotonin to communicate with each other, and secondly, drug use can affect other serotonin in the brain,” explained Dr. Hiroaki Hamada, a former doctoral student in the Research Unit. OIST Neural Computing and lead author of a paper on this topic. study published in the journal Nature Communications.
Previous studies by researchers at the Neural Computing Unit have shown that serotonin neurons in the DRN promote adaptive behaviors in mice associated with future rewards. Dr. Hamada and his collaborators wanted to understand the brain mechanisms that cause these adaptive behaviors.
“We knew that DRN serotonin activation has strong effects on behavior, but we didn’t know how this serotonin activation affects different parts of the brain,” said Professor Kenji Doya, leader of the Neural Computing Unit.
Looking at the whole-brain response to DRN serotonin activation
The researchers used a novel technique called optofunctional MRI to address this question. They used a method called optogenetics to selectively activate serotonin neurons in the DRN with light and observed the whole-brain response using fMRI (magnetic resonance imaging). They used the latest MRI scanner with a strong magnetic field to achieve the high resolution needed to study the small brains of mice. The mice were placed in an MRI scanner and serotonin neurons were stimulated at regular intervals to see how this affected the entire brain.
They found that DRN serotonin stimulation causes activation of the cerebral cortex and basal ganglia, areas of the brain involved in many cognitive functions. This result was very different from a previous study conducted under anesthesia. Furthermore, the brain’s response to serotonin stimulation is strongly related to the distribution of serotonin receptors (serotonin-activated proteins) and the connection patterns of DRN serotonin neurons.
“We clearly see on high-field MRI images which areas of the brain activate and deactivate during the awake state and under anesthesia when we activate serotonin neurons in the DRN,” Dr. Hamada said. “A previous study showed that the cerebral cortex and basal ganglia were largely deactivated under anesthesia, which we also observed, but in the awake state these areas are significantly activated.”
The cerebral cortex and basal ganglia are parts of the brain critical to many cognitive processes, including motor activity and behaviors to obtain rewards such as food and water. Therefore, activation of DNR serotonergic neurons can lead to changes in motivation and behavior.
Patience and stimulation of your own serotonin.
The combination of the new high-field MRI technique and optogenetics presented many obstacles that Dr. Hamada had to overcome. “We introduced and adapted a method previously used by our collaborators and established many new procedures at OIST. For me, the main challenge was using the new MRI machine at that time, so I needed to be patient and stimulate my own serotonin. I started After that I exercise a lot,” he laughs.
Seeing activations at the DRN for the first time was a highlight for Dr. Hamada. At first he used the same intensity of light as his collaborators, but it was too weak to see brain responses on the MRI. He then used larger optical fibers and increased the intensity to stimulate the DRNs.
Professor Doya noted that the next important milestone to reach is to understand exactly how this activation of serotonin occurs throughout the brain: “It is important to discover what the actual molecular mechanism is that allows this activation in our brain. People who would like to improve” “Adjusting your behavior and thinking in different situations could also be helpful in learning more about how serotonin helps control our mood.”