summary: A new study has revealed how activating the brain’s serotonin centre affects the behaviour and motivation of awake mice. Using optogenetics and high-field MRI, researchers discovered that stimulating serotonin neurons in the dorsal raphe nucleus (DRN) activates the cerebral cortex and basal ganglia, areas important for cognitive function.
“This study highlights the complex role of serotonin in whole-brain activation and its effects on behavior and mood. These findings may improve our understanding of mood medications and behavioral adaptation.”
Key Facts:
- Innovative TechnologyThe researchers used optogenetics and high-field MRI to study serotonin activation in awake mice.
- Brain activationDRN serotonin stimulation activates the cerebral cortex and basal ganglia, influencing motivation and behavior.
- Treatment InsightsUnderstanding the role of serotonin in brain activation may lead to improved mood therapy and behavioral adaptation strategies.
sauce: Okinawa Institute of Science and Technology Graduate University
Our brains are made up of tens of billions of nerve cells called neurons. These cells communicate with each other through biological molecules called neurotransmitters.
Serotonin, a neurotransmitter, is produced by serotonin neurons in the brain and influences many of our behaviors and cognitive functions, including memory, sleep, and mood.
Scientists at the Okinawa Institute of Science and Technology (OIST) and collaborators at the Keio University School of Medicine used mice to study the dorsal raphe nucleus (DRN), the main source of serotonin in the brain.
The study, the first to examine the effects of activating the brain’s “serotonin center” in awake animals, found that serotonin from the DRN activates areas of the brain that influence behavior and motivation.
“Learning about the brain’s serotonin system can help us understand how we adapt behavior and how mood therapy drugs work. But it has been difficult to study how serotonin from the DRN affects the entire brain.”
“First, because electrical stimulation of the DRN might also activate neurons that don’t use serotonin to communicate with each other. Secondly, drug use might affect other serotonins in the brain,” explains Dr. Hiroaki Hamada, a former doctoral student in the OIST Neural Computation Unit.
Dr. Hamada is lead author on a paper about the study, which has been published in the journal Neurology. Nature Communications.
Previous work by researchers in the Neural Computation Unit has shown that serotonin neurons in the DRN promote adaptive behaviors linked to future rewards in mice. Dr. Hamada and his collaborators wanted to understand the brain mechanisms that drive these adaptive behaviors.
“We knew that DRN serotonin activation has a strong effect 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 Computation Unit.
Observing whole-brain responses to DRN serotonin activation
To answer this question, the researchers used a new technique called optical functional MRI: They used a method called optogenetics to selectively activate serotonin neurons in the DRN with light, then used functional MRI (magnetic resonance imaging) to observe the response throughout the brain.
They took advantage of state-of-the-art MRI scanners with powerful magnetic fields that gave them the high resolution they needed to study the tiny brains of mice. They placed the mice in the MRI scanner and stimulated their serotonin neurons at regular intervals to see how this affected the brain as a whole.
The researchers found that DRN serotonin stimulation caused activation of the cerebral cortex and basal ganglia, brain regions involved in many cognitive functions, a result that differed significantly from previous studies conducted under anesthesia.
Furthermore, the brain’s response to serotonin stimulation is strongly linked to the distribution of serotonin receptors (proteins activated by serotonin) and the connectivity pattern of DRN serotonin neurons.
“The high-field MRI images clearly show which areas of the brain are activated and which areas are deactivated when serotonin neurons in the DRN are activated during wakefulness and anesthesia,” Dr. Hamada said.
“Previous studies have shown that the cerebral cortex and basal ganglia are largely inactive under anesthesia, and we observed that. However, in the awake state, these regions are significantly more active.”
The cerebral cortex and basal ganglia are parts of the brain that are important for many cognitive processes, including motor activity and behaviors that lead to rewards such as food and water. Therefore, activation of DNR serotonin neurons may lead to changes in motivation and behavior.
Patience and serotonin stimulation
Combining the new technologies of high-field MRI and optogenetics presented many obstacles that Dr. Hamada had to overcome.
“We introduced and improved methods previously used by our collaborators 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 stimulate my serotonin. After that, I started doing a lot of exercise,” he said.
For Dr. Hamada, seeing DRN activation for the first time was an unforgettable moment. Initially, he used the same light intensity as his collaborators, but it was too weak to see the brain’s response in an MRI. So he used a larger optical fiber and increased the intensity to stimulate the DRN.
Doya noted that the next important milestone to achieve is to understand exactly how serotonin activation occurs throughout the brain.
“It will be important to determine what the actual molecular mechanisms are that enable this activation in the brain.
“People who want to better regulate their behavior and thoughts in different situations may also benefit from learning more about how serotonin controls mood.”
Research news on serotonin, motivation, and behavior
author: Hiroaki Hamada
sauce: Okinawa Institute of Science and Technology Graduate University
contact: Hiroaki Hamada – OIST
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Optogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation“Current Status and Issues of Biotechnology in Japan” by Hiroaki Hamada et al. Nature Communications
Abstract
Optogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation
Serotonin is a neuromodulator that influences a variety of behavioral and cognitive functions, but how serotonin elicits such diverse effects via its projections and different receptors throughout the brain remains unclear.
Here, we used functional MRI with an 11.7 T scanner and a cryoprobe to measure whole-brain responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain.
Transient activation of DRN serotonin neurons evoked activation throughout the brain, including the medial prefrontal cortex, striatum, and ventral tegmental area.
The same stimulation administered under isoflurane anesthesia reduced activation throughout the brain, including the hippocampal complex.
These brain-wide response patterns can be explained by a DRN serotonin projection topography and serotonin receptor expression profile with enhanced weighting of 5-HT1 receptors.
Together, these results provide insight into the DR serotonergic system, which is consistent with recent findings regarding its function in adaptive behavior.
