Orexin neurons link reward expectation to sustained effort in rats

Researchers at Nagoya University have identified a specific group of brain cells that help translate the expectation of a reward into the willingness to keep working for it. The study, published in Proceedings of the National Academy of Sciences, focused on orexin neurons, which are already known to regulate sleep, appetite and energy use.

To test the neurons' role in motivation, the team created genetically modified "orexin-Cre" rats that allowed precise targeting of these cells. Rats were placed in a progressive ratio task where they had to make an increasing number of touches to receive each food pellet. The point at which a rat stopped trying, called the breakpoint, served as a measure of motivational strength.

When researchers used chemogenetics to activate orexin neurons, the rats reached higher breakpoints, indicating they would work harder for the reward. Conversely, rats in which orexin neurons were selectively degenerated gave up sooner, showing weaker motivation.

Fiber photometry recordings revealed that orexin neuron activity rose as the animals anticipated a reward and fell after receiving it. If an expected reward failed to appear, activity remained elevated. The response also grew stronger as the required effort increased, suggesting the neurons encode both reward expectation and the cost of obtaining it.

Using optogenetics to suppress orexin neurons at the moment of reward expectation caused rats to take longer on effortful tasks and lowered their breakpoints. However, artificially increasing neuron activity beyond normal levels did not boost motivation further, indicating the cells are necessary but not sufficient on their own to enhance drive.

The researchers plan to map the circuits that send signals to and receive signals from orexin neurons. A clearer picture of this network could eventually inform approaches to motivational deficits seen in conditions such as depression, addiction and ADHD.

The work was supported by multiple Japanese research foundations and agencies, including the Japan Agency for Medical Research and Development and the Japan Society for the Promotion of Science.