The quality of brainstem serotonin

New insights into the opposite effects of serotonin-producing nerve fibers in mice could lead to drugs
to treat addiction and major depressive disorder.

Japanese scientists have discovered a neural pathway
in mice involved in processing rewards and painful stimuli and situations.

This new pathway originates from a bundle of brainstem nerve fibers called the median suture nucleus, as opposed to
the previously identified reward/aversion pathway originating in the nearby dorsal suture nucleus.
The findings, published by scientists at Hokkaido University and Kyoto University and colleagues in Nature Communications, could have implications for developing drug treatments for a variety of mental disorders, including addiction and major depressive disorder
.

Previous studies have revealed that activating the nerve fibers that produce serotonin in the dorsal suture nucleus in the brainstem of mice leads to reward-associated pleasurable sensations
.
However, selective serotonin reuptake inhibitors (SSRIs), an antidepressant drug that increases serotonin levels in the brain, does not produce a clear sense of reward and does not treat the loss
of the ability to feel pleasure associated with depression.
This suggests that there are other serotonin-producing neural pathways in the brain that are associated
with feelings of reward and disgust.

To further investigate the brain's reward and aversion neural pathways, Hokkaido University neuropharmacologist Yu Ohmura and Kyoto University pharmacologist Kazuki Nagayasu, along with colleagues at several Japanese universities, focused their attention on
the middle suture nucleus.
This region has not received as much research attention as its brainstem neighbor, the dorsal suture nucleus, although it is also a source of
serotonergic nerve fibers.

By using fluorescent proteins to detect the entry of calcium ions, the scientists performed a variety of tests to measure the activity of mouse serotonin neurons to stimulate and inhibit the middle suture, which is a proxy
for neuronal activation in cell type-specific ways.

For example, they found that pinching a mouse's tail—an unpleasant stimulus—increased calcium-dependent fluorescence
in serotonin neurons in the middle slit.
On the other hand, giving mice foods such as sugar can reduce serotonin fluorescence
in the middle seam.
In addition, direct stimulation or inhibition of the middle suture nucleus, using genetic techniques involving light, leads to disgust or reward-seeking behaviors, such as avoidance or wanting to stay in a room, depending on the type of
stimulus applied.

The team also conducted tests to discover where the serotonergic nerve fibers opened in the middle of the middle suture send their signals and found an important connection
to the intersuture nucleus of the brainstem.
They also determined that serotonin receptors within this nucleus are involved in aversive properties
associated with serotonergic activity in the intermediary line.

Further research is needed to fully elucidate this and other pathways
related to feelings and behaviors of reward and disgust.
"These new insights may lead to a better understanding of the biological basis of mental disorders, in which abnormal handling of reward and aversion information occurs, such as in drug addiction and major depressive disorder
," Nagaya said.