Fiber photometry technique reveals brain serotonin levels increase with reward value

Serotonin is often called the “happiness molecule”. It plays a vital role in changing mood and is also a neurotransmitter that sends signals to the brain and body.

Researchers generally believe that this chemical plays an overall role in modulating brain states by acting over a longer period of time than dopamine, which signals reward but acts over a much shorter period.

Now, a Dartmouth study published in The Journal of Neuroscience reports that serotonin increases in anticipation of a reward and scales with the value of that reward.

For decades, previous research has studied the release of dopamine levels when encoding the value of rewards on a sub-second time scale, using a technique that allows scientists to monitor it in different areas of the brain from mouse.

Techniques for monitoring serotonin on this time scale did not previously exist, leaving many unknowns about when serotonin is released into the brain due to its widespread projections. Serotonin is an extraordinarily complex system, with cells located in a small region of the brain, which then send their messages to almost every other area of ​​the brain.

There are 14 serotonin receptors, which are like 14 different locks and the key, serotonin, can fit into any of these locks, unlocking a different message depending on the door. This explains why previous studies focused on targeting these receptors before it was possible to examine serotonin itself.

“In this research, we used a new biosensor called GRAB-serotonin, which could, for the first time, measure the molecule by “capturing” the serotonin released in the brain, while the mouse ran around receiving a delicious treat. ” says lead author Kate Nautiyal, assistant professor of psychological and brain sciences at Dartmouth.

Using a technique called fiber photometry, light can be used to trigger and then measure fluctuations in the fluorescence of a biosensor like GRAB, whenever serotonin is detected. The team was able to study the release of serotonin in the mice as they received rewards, which in this case were varying concentrations of condensed milk, which the mice love. The researchers were then able to observe how serotonin levels changed depending on the quality of the reward.

“We understood pretty well that if you change serotonin signaling by targeting receptors or manipulating reuptake, like with selective serotonin reuptake inhibitors, which are used in antidepressants, you get these big impacts on the “mood and can change the way animals or individuals appear to regulate behavior,” says co-author Mitchell Spring, a postdoctoral researcher who worked on this project at the Nautiyal Lab, a behavioral neuroscience laboratory in the Department of Psychological Sciences and brain studies from Dartmouth.

The results showed that consuming higher concentrations of reward was associated with greater serotonin release. When the mice were thirsty and given water, there was a strong serotonin signal, and when they were satisfied with a good reward and full, the serotonin signal was not as strong.

The results also showed that if you give mice a cue that predicts reward, serotonin levels increase during the cue, or anticipation, of reward.

“We found that it was possible to modulate the serotonin signal with the subjective value of the reward,” says Nautiyal. “Our results tell us that serotonin is actually a signal in the brain that monitors the quality of a reward.”

By measuring serotonin release, the team focused on a region of the brain, the dorsomedial striatum, that was previously very strongly associated with dopamine, decision-making and impulsivity.

Researchers say that selective serotonin reuptake inhibitors are widely prescribed and generally effective, but we don’t fully understand how they work or what serotonin does to treat the behaviors treated by these antidepressants.

“A better understanding of how serotonin functions at baseline or in healthy individuals during a positive experience could be used to develop more targeted treatments for psychiatric disorders like depression and addiction,” says Nautiyal.