What are orexin neurons? Scientists discover brain cells that help sustain motivation when rewards become harder to reach

New research identifies orexin neurons as key brain cells that may help sustain effort when rewards become harder to obtain offering clues about motivation.

Orexin neurons.

Wondering what makes it easy to keep going toward a goal when the reward becomes harder to achieve? A group of researchers at Nagoya University in Japan has discovered a mechanism in the brain where orexin cells help maintain motivated behaviour when greater effort is needed. The results published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) revealed that lack of motivation is a normal symptom of depression, addiction and ADHD. However scientists do not fully understand the brain processes involved in motivational difficulties.

Where are Orexin Neurons found?

Orexin neurons are specialised cells in the brain that produce orexin which is a chemical messenger involved in controlling important functions such as sleep, appetite and energy expenditure. Previous research has indicated that such neurons could also play a role in motivation but what that role was unclear. The study was spearheaded by associate professor Hiroyuki Mizoguchi and professor emeritus Kiyofumi Yamada at Nagoya University's Graduate School of Medicine.

How did the researchers study motivation?

The scientists performed genetic modification on "orexin-Cre" rats enabling them to specifically target and modify the orexin-producing neurons. The rats were then transferred to a progressive ratio test that required an increasing number of touches to obtain each food reward. The breakpoint or the point at which the animals ceased to work was used as a measure of motivational power. During the experiments the team selectively suppressed, monitored and activated orexin neurons using chemogenetics, fiber photometry and optogenetics.

Orexin activity increased

The activation of orexin neurons resulted in higher breakpoints indicating that the rats were willing to work more in order to obtain the food reward. This was the opposite case when selective degeneration of orexin neurons was carried out. The rats reached lower breakpoints suggesting a decrease in motivation. The scientists also tracked the live neurons. During anticipation of the reward there was a rise in orexin and a fall in orexin after food delivery but if a hope for reward didn't come activity stayed high. Importantly orexin activity became stronger as the amount of work required to obtain the reward increased. Researchers said this pattern could suggest that orexin neurons link reward anticipation to the work involved in securing the reward.

Blocking orexin decreased motivation

Now the researchers manipulated orexin neurons when the rats were anticipating a reward. When they were blocked from their activity they took longer to complete effort-based tasks and their breakpoints were lower. Raising orexin activity didn't increase their effort though while the neurons were successfully fired there was no further development of motivated behaviour. This indicates that orexin neurons are required for motivation but that raising their firing rate above normal may not lead to an increase in motivation. The results provide novel insights into the mechanisms by which the brain maintains goal-directed behaviour when rewards become less frequent. Future studies will explore the circuits that control orexin neurons. Gaining insight into the pathways could one day enable researchers to explore motivational challenges.

Disclaimer: This content is for informational purposes only and does not establish that orexin neurons directly cause motivational disorders or that these findings apply to humans.