Group Leader

Jing Ren

Developmental assembly of the serotonin system

Jing Ren
Group Members
  • Chui Kuen (Zora) Chan
  • Jingwen Liang
  • Cheng Qi
  • Kenneth Wu

The serotonin system is one of the brain’s most expansive neural systems, influencing mood, cognition, emotion and sleep. It is strongly linked to mental disorders like depression and anxiety and is the primary target of many psychiatric medications. Despite its importance, how this system forms during development and how disruptions contribute to mental illness remain unclear.

Recent research from our group has shown that the serotonin system is not a single, uniform network but is instead made up of distinct subsystems, each targeting specific areas of the brain and affecting different behaviours.

We are investigating the behavioural functions of long-range and local connections within the forebrain-projecting serotonin system. Our work will help reveal how serotonin wiring is established, how it can go awry in psychiatric disorders and how we might better target it for treatment.

Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems
The dorsal raphe nucleus serotonin system contains subsystems that differ in connectivity, physiological responses and behavioural functions.

We also aim to uncover how these sub-systems form. Using machine learning tools, we created a 3D whole-brain map that tracks serotonin connectivity over time. Combined with single-cell genetic profiling, this allowed us to trace serotonin neuron subtypes from the embryonic stage to adulthood. We found that diversity emerges early, with each subtype following a genetically programmed wiring pattern.

Fly-through coronal serotonin neuron fibre density heatmaps along the A-P axis at six selected post-natal stages.

To enhance brain mapping, we developed D-LMBmap, a deep-learning tool that automates whole-brain connectivity analysis and eliminates the need for tedious manual work. Building on this, D-LMBmapX enables high-resolution tracking of brain circuit development across postnatal stages, providing new insights into serotonin and other neural systems.

Selected Publications

D-LMBmapX: Generalised Deep Learning Pipeline for 5D Whole-brain Circuitry ProfilingLi Z, Li P, Pan H, Adams AMJ, Huang Z, Su Y, Liu H, Li J, Zhong B, Su Y, Bray L, Sturgess RN, Li C, Zhu J, Zhang D, Zhang S, Ren JbioRxiv: (2025) preprint
D-LMBmap: a fully automated deep-learning pipeline for whole-brain profiling of neural circuitry.Li Z, Shang Z, Liu J, Zhen H, Zhu E, Zhong S, Sturgess RN, Zhou Y, Hu X, Zhao X, Wu Y, Li P, Lin R, Ren JNat Methods 20(10): 1593-1604 (2023)
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei.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 LElife 8: (2020) Epub
Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub‑systems.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 LCell 175(2): 472-487.e20 (2019)