What makes an individual wait much longer while other jittery, is still a debated area. Brain areas that specifically secrete serotonin to regulate the patience level of an individual have been identified as per research by scientists at the Neural Computation Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), published in the journal Science Advances.
"Serotonin is one of the most famous neuromodulators of behavior, helping to regulate mood, sleep-wake cycles, and appetite," said Dr. Katsuhiko Miyazaki, the author of the study. "Our research shows that the release of this chemical messenger also plays a crucial role in promoting patience, increasing the time that mice are willing to wait for a food reward."
The team used optogenetics - a technique that uses light via an optical fiber, implanted in the brain to stimulate specific neurons, in a genetically engineered mouse. The serotonin-releasing neurons in the mice would then express a light-sensitive protein upon stimulation.
The researchers demonstrated that the mice waited much longer for the food (reward) when the serotonin-secreting neurons were stimulated. "In other words, for the serotonin to promote patience, the mice had to be confident that a reward would come but uncertain about when it would arrive," says Dr. Miyazaki, the author of the study.
The scientists explored the dorsal raphe nucleus - the central hub of serotonin-releasing neurons along with its three other connective areas of the brain - a deep brain structure called the nucleus accumbens, and two parts of the frontal lobe called the orbitofrontal cortex and the medial prefrontal cortex, to find out their role in regulating patience. The areas were implanted with optical fibers.
The latter three areas are also involved in increasing the impulsive behavior of a person. "Impulse behaviors are intrinsically linked to patience - the more impulsive an individual is, the less patient - so these brain areas were prime candidates," explained Dr. Miyazaki.
The mice were then trained to perform a waiting task. The mice had to keep their nose held inside a hole - "nose poke" until a food pellet was given. 75% of the trials were rewarded at a fixed timing of 10-6 secs after holding at the nose poke and also with varied timing. In 25% of trials, called the omission trials, the mice were not rewarded but they were measured for patience - how long nose poke was held when serotonin-releasing neurons were and were not stimulated.
On stimulating the serotonin-releasing neural fibers of nucleus accumbens, there was no increase in waiting time. Whereas, stimulating the medial prefrontal cortex and the orbitofrontal cortex made the mice wait much longer, the latter having more similar results to the dorsal raphe nucleus.
Computational models were used to confirm the internal model of the timing of reward delivery in mice. The dorsal raphe nucleus increased the reward probability from 75% to 94% in both the orbital frontal cortex and the medial prefrontal cortex, making the mice wait much longer. This proved that the reward system of the dorsal raphe nucleus works as a complementary system to the orbital frontal cortex and the medial prefrontal cortex.
The study enhanced the understanding of the role of brain areas in regulating serotonin, which would aid in the development of anti-depressive drugs - also known as serotonin reuptake inhibitors (SSRIs). SSRIs increase the levels of serotonin to overcome depression in patients.
"This is an area we are keen to explore in the future, by using depression models of mice," said Dr. Miyazaki. "We may find under certain genetic or environmental conditions that some of these identified brain areas have altered functions. By pinning down these regions, this could open avenues to provide more targeted treatments that act on specific areas of the brain, rather than the whole brain."