Orexin Neurons May Help Rats Stay Motivated for Food Rewards

Motivation – or its absence – influences daily life in both major and minor ways. Whether we are changing careers or simply switching television channels, our choices are steered by what drives us and by what we consider rewarding.

A new study in PNAS, led by researchers at Nagoya University in Japan, identifies neurons that produce the chemical orexin as important contributors to food-reward motivation in rats.

These cells sit in the brain's hypothalamus. Earlier research has associated them with wakefulness, energy use and, indeed, motivation. The team behind the new work set out to examine that motivational connection more closely.

"A potential mechanism for translating expectations into sustained action."

– Neuroscientist Hiroyuki Mizoguchi

Orexin neurons and food-reward motivation in rats

The experiments revealed orexin's moment-by-moment influence, showing how closely it is involved in judging whether a reward is worth the effort needed to obtain it – an essential calculation for motivation.

Watch the study video on YouTube

"Our observations highlight that orexin activities are implicated in the motivational process in rats and that dynamic changes in activation of orexin neurons may be involved in reward-seeking behavior based on reward prediction," the researchers write in their published paper.

"In particular, orexin neuron response depends on degree/size of effort; these changes may indicate expectation for incentive against one's efforts."

Using genetic modifications, the researchers could artificially increase or restrict the activity of orexin-producing neurons. During food-reward tests, rats worked harder to obtain food when orexin neurons were activated, but abandoned the task sooner when those neurons were inhibited.

Real-time observation of naturally occurring orexin neuron activity also found that it rose before the rats received a reward, then fell once they had received it. When an anticipated reward failed to arrive, orexin activity stayed elevated.

The more work the rats had to do for a reward, the greater the activity in these neurons. This indicates that orexin activity could potentially serve as a marker for the effort involved in seeking an expected reward.

"Our study demonstrated significant changes in orexin neuron activity depending on expected rewards and the effort required, suggesting a potential mechanism for translating expectations into sustained action," says neuroscientist Hiroyuki Mizoguchi of Nagoya University.

How orexin activity may sustain motivation

In additional experiments, the team controlled orexin neuron activity while rewards were expected. Lowering that activity appeared to lessen motivation, while raising it did not correspond with greater motivation.

It may be that these neurons help maintain motivation at a particular baseline, rather than acting precisely like a control that can simply be turned up or down.

"Therefore, orexin is crucial for linking predicted expectations with motivated behavior," the researchers write. "Moreover, optimization of orexin activity is necessary to overcome difficulties during motivated behaviors."

Naturally, these findings must still be translated to the human brain. Humans also possess an orexin system, however, making this a significant question for future research into committing to a task and remaining committed to it.

Disrupted motivation is associated with several mental disorders, including depression and addiction. Learning more about the workings of orexin in the brain could therefore also improve treatment of these conditions.

That prospect remains some distance away. The researchers next intend to investigate the incoming and outgoing brain circuits connected to orexin neurons, to establish the natural sequence of events that switches them on or off.

Related: One Brain Chemical May Be Key to Breaking a Habit, Study Finds

Implications for motivation and mental health

Because motivation is such a basic force behind behaviour, any fresh insight into its workings is likely to have broad implications.

"A better and further understanding of orexinergic mechanisms underlying motivated behaviors would provide insights into the ways that motivation can be developed, and the disorders can be overcome," the researchers write.

The research was published in Proceedings of the National Academy of Sciences.

This article was fact-checked and edited by Rebecca Dyer. Although we take pride in our process, we are only human. If you notice an error, please let us know.