International Business Department           Liu Bojia           October 28, 2024

  In the 1950s, Swedish neuroscientist Arvid Carlsson discovered that dopamine could play an important role in the brain as a neurotransmitter. Decades on, numerous studies have revealed a wide range of dopamine's roles, including the regulation of motor, cognitive, learning and reward-oriented behaviours. When the brain is deficient in dopamine, physical mobility and memory are affected. Parkinson's disease, for example, is caused by the degeneration and death of dopaminergic neurons in the substantia nigra, and patients suffer from tremors, slowed movements and balance disorders, as well as declining cognitive and autonomic functions. Therefore, understanding the mechanism of action of dopamine is expected to lead to a new treatment for Parkinson's disease.

  Currently, the prevailing view is that dopamine transmits signals through rapid release to regulate movement and cognition. With the application of the Parkinson's treatment drug levodopa, research data show that levodopa can effectively improve movement disorders, but has little effect on cognitive symptoms, suggesting that the mechanisms by which dopamine regulates movement and cognition may be different.

  Just recently in the journal Nature, researchers from Harvard Medical School found that the process of initiating exercise does not rely on the rapid release of dopamine, but is instead regulated by the slow release of dopamine activity. Reward-directed behaviours, including those related to learning and motivation, on the other hand, rely on the rapid release of dopamine to regulate the action. This also rewrites past perceptions of dopamine and motor regulatory mechanisms.

  To explore the association between dopamine release patterns and various behaviours, the authors constructed a batch of genetically engineered mice whose dopaminergic neurons would be deficient in a key protein, RIM, which is important for regulating dopamine release. According to the observations, mice lacking RIM essentially lost the dynamic process of rapid dopamine release but maintained basal dopamine release levels compared to wild-type control mice.

  And in subsequent behavioural tests, the authors found that there was no difference in spontaneous motor function between the two groups of mice, and that even though the mice lacked the RIM protein and were unable to achieve rapid dopamine release, they still performed well in various types of motor behavioural tests, such as free movement in a large field or climbing objects.

  However, in some reward-directed learning behaviours, such as tests that associate water sources and food with specific locations and smells, mice lacking the RIM protein usually perform poorly, and they rarely drink from water sources that are reward-inducing in nature. This suggests that impaired rapid release of dopamine affects this type of behaviour.

  And in another experiment, the authors constructed a batch of dopamine-deficient mice that had an impaired ability to initiate movement, similar to the symptoms seen in Parkinson's disease patients. They then gave the experimental mice levodopa treatment. Dopamine levels were elevated in the treated mice, and significant improvements in motor function occurred, but the rapid release of dopamine in the mice's brains was still not restored. This explains why levodopa had a limited effect on improving cognitive and learning functions.

  The researchers noted that understanding the relationship between different behaviours and dopamine release could help develop more precise Parkinson's disease treatments, such as levodopa's ability to restore motor-initiated behaviours, while there are also molecules that can reactivate the rapid release of dopamine, which are expected to help improve cognitive and learning behaviours.