The serotonin system is the most frequently targeted neural system for treating mental illnesses, including depression and anxiety. These mental illnesses are among the leading causes of disability globally, affecting one in four people in the world.
Our team focuses on bridging the huge gap on the link between the abnormalities of serotonergic wiring and transmission, and the vulnerability to mental illnesses.
Circuitry Assembly of the Midbrain Serotonin System
The serotonin (5HT) system is believed to be the most expansive neural system, innervating nearly every area of the brain and has been implicated in the modulation of seemingly every human behaviour. Strikingly, despite its imposing breadth of influence, the serotonin system originates from a very small proportion of neurons, which constitute only 1/200,000 of all CNS neurons. How is the serotonin system organized to manage such a broad range of modulation? We recently revealed that there are anatomically defined parallel serotonin sub-systems that exert different influences on distinct behavioural functions of mice. Furthermore, we elucidated the molecular architecture of these sub-systems.
The next key questions that intrigue us are: How is the organization of the serotonin system determined during development, and how do disruptions in these developmental programs alter this organization, and thereby possibly contribute to the pathology of mental illnesses?
Co-release Modulation of the Midbrain Serotonin System
Colocalization of small-molecule and neuropeptide transmitters is prevalent throughout the nervous system of all animals. In addition, the traditional view that one neuron releases only one classical neurotransmitter has given way to the new understanding of many neurons in adult mammalian brain co-release multiple small-molecule neurotransmitters. However, the physiological role for co-transmission has remained poorly understood and it is still unknown how the release of co-existing transmitters is modulated. We will use the serotonin system as the module system to investigate how multiple transmitters’ co-release is modulated, and how abnormal transmission of serotonin system influences behaviours.