The serotonin (5HT) system is the most frequently targeted neural system pharmacologically for treating psychiatric disorders, including depression and anxiety. It is the most expansive neural system, innervating nearly every area of the brain and has been implicated in the modulation of seemingly every human behaviour. The key questions we focus on are: how is the serotonin system organized to manage such a broad range of modulation? 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?

We recently revealed that individual raphe nucleus contains anatomically defined parallel serotonin sub-systems that exert different influences on distinct behavioural functions of mice. We are trying to determine how individual serotonin sub-system reaches their particular target brain regions during development in mice. We shall identify the molecules that guide the neural circuit formation. After that, we shall combine multiple advanced tools to understand when some of the serotonin sub-systems fail to connect with their downstream brain regions: which aspects of the mental states are disrupted. This work will advance our understanding of the relationship between neurodevelopment and psychiatric disorders, with the potential of discovering novel targets for therapeutic interventions.

References

Ren J.*#, Isakova A.#, Friedmann D.#, Zeng J.#, Grutzner SM, Pun A, Zhao GQ., Kolluru SS., Wang R., Lin R., Li P., Li A., Raymond JL., Luo Q., Luo M., Quake SR., Luo L.*. (2019)
Serotonin Neurons in Midbrain Raphe Nuclei: from Single Cell Transcrpitomes to Whole-Brain Projections.
BioRxiv, 674697. # These authors contributed equally. * Corresponding authors.

Ren J., Friedmann D., Xiong J., Liu CD., Ferguson BR., Weerakkody T., DeLoach KE., Ran C., Pun A., Sun Y., Weissbourd B., Neve RL., Huguenard J., Horowitz MA., Luo L. (2018)
Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems.
Cell 175(2): 472-487. E20.