Summary: Stimulation of the serotonergic center of the brain, the dorsal raphe nucleus (DRN), activates areas responsible for behavior and motivation. This discovery, using opto-functional MRI in awake mice, highlights the important role of serotonin in cognitive functions.
The study offers insight into how serotonin influences behavior and mood regulation.
Highlights:
- DRN serotonin activation stimulates the cerebral cortex and basal ganglia.
- High-field MRI and optogenetics reveal whole-brain effects of serotonin in awake mice.
- The results could advance the understanding of mood disorders and behavioral adaptations.
Source: OIST
Our brain is made up of tens of billions of nerve cells called neurons. These cells communicate with each other using biomolecules called neurotransmitters. Serotonin, a type of neurotransmitter, is produced by serotonergic neurons in our brain and influences many of our behavioral and cognitive functions such as memory, sleep and mood.
Using mice, scientists from the Okinawa Institute of Science and Technology (OIST) and their collaborators at Keio University School of Medicine 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 serotonin from the DRN activates areas of the brain that affect behavior and motivation.
“Learning more about the brain’s serotonergic 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 second, drug use can affect other serotonins in the brain,” explained Dr. Hiroaki Hamada, former doctoral student at OIST Neural Computing Unit and lead author of an article on this study published in the journal Natural communications.
Previous studies by researchers in the Neural Computation Unit have shown that serotonin neurons in the DRN promote adaptive behaviors associated with future rewards in mice. Dr. Hamada and his collaborators wanted to understand the brain mechanisms behind these adaptive behaviors.
“We knew that DRN activation of serotonin had important effects on behavior, but we did not know how this serotonin activation affects different parts of the brain,” said Professor Kenji Doya, head of the unit. of neural calculation.
Observe the whole-brain response to DRN serotonin activation
Researchers used a new technique called opto-functional MRI to answer this question. They used a method called optogenetics to selectively activate serotonergic neurons in the DRN with light and observed the whole brain’s response using functional MRI (magnetic resonance imaging).
They used the latest MRI scanner with a powerful magnetic field to achieve the high resolution needed to study small mouse brains. The mice were placed in an MRI scanner and the serotonergic 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, brain areas involved in many cognitive functions. This result was very different from a previous study carried out under anesthesia.
Additionally, the brain’s response to serotonin stimulation is strongly linked to the distribution of serotonin receptors (serotonin-activated proteins) and the connection patterns of DRN serotonin neurons.
“We see clearly from 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,” Dr. Hamada said.
“A previous study showed that the cerebral cortex and basal ganglia were mostly deactivated under anesthesia, which we also observed. However, in awake states, these areas are significantly activated.”
The cerebral cortex and basal ganglia are parts of the brain essential for many cognitive processes, including motor activity and behaviors to obtain rewards such as food and water. Activation of DNR serotonergic neurons can therefore lead to changes in motivation and behavior.
Patience and stimulating 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 colleagues and established many new procedures at OIST. For me, the main challenge at the time was using the new MRI machine, so I had to be patient and boost my own serotonin. After that, I started exercising a lot,” he laughed.
Seeing the activations in the DRN for the first time was a defining moment for Dr. Hamada. At first, he used the same light intensity that his collaborators used, but it was too weak to see the brain responses in the MRI. He then used larger optical fibers and increased the intensity to stimulate the DRNs.
Professor Doya noted that the next important step is to understand exactly how this brain-wide activation of serotonin occurs: “It is important to find out what the actual molecular mechanism is that allows this activation in our brain.
“People who want to better adjust their behavior and thinking in different situations might also find it helpful to learn more about how serotonin helps control our moods.”
About this news on serotonin research, behavior and motivation
Author: Tomomi Okubo
Source: OIST
Contact: Tomomi Okubo – OIST
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Optogenetic activation of serotonergic dorsal raphe neurons induces brain-wide activation” by Hiroaki Hamada et al. Natural communications
Abstract
Optogenetic activation of serotonergic dorsal raphe neurons induces brain-wide activation
Serotonin is a neuromodulator that affects several behavioral and cognitive functions. However, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear.
Here, we measured whole-brain responses to optogenetic stimulation of serotonergic neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7 T scanner and a cryoprobe.
Transient activation of DRN serotonergic neurons caused brain-wide activation, including the medial prefrontal cortex, striatum, and ventral tegmental area. The same stimulation under isoflurane anesthesia decreased brain-wide activation, including the hippocampal complex.
These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with increased weightings on 5-HT1 receptors.
Together, these results provide insight into the DR serotonergic system, which is consistent with recent findings of its functions in adaptive behaviors.