WeiGuang Li-INSTITUTE FOR TRANSLATIONAL BRAIN RESEARCH

WeiGuang Li

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WeiGuang Li Principal Investigator

Memory Dynamics and Physiology

Dr. Wei-Guang Li is currently a Principal Investigator and professor at the Institute for Translational Brain Research, Fudan University. He received his bachelor degree in Basic Medicine at Sichuan University in 2006. He received his Ph.D. degree in Neurobiology at Institute of Neuroscience, Chinese Academy of Sciences in 2011. He then went to Shanghai Jiao Tong University School of Medicine for postdoctoral training and was appointed as a faculty member there in 2014 (from assistant investigator, associate investigator to investigator). In September 2021, he joined Fudan University and established a laboratory entitled “Memory Dynamics and Physiology”. He is dedicated to uncovering the neural mechanisms underlying memory formation, updating, and behavioral regulation, elucidating how memory dysfunction drives the progression of brain disorders, and developing precision interventions guided by memory principles. His previous work has been published as the corresponding (including co-corresponding) author in Nature Neuroscience, Journal of Clinical Investigation, Nature Communications, Science Advances, National Science Review, Molecular Psychiatry, and other academic journals.

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Memory provides the foundation for accumulating experience, acquiring knowledge, mastering skills, and guiding behaviors. Research on memory requires not only understanding how experiences are encoded, stored, and retrieved, but also elucidating how memories dynamically balance stability and plasticity, how distinct memories interact to form abstract representations, and how the brain uses prior experiences to infer current states, predict potential outcomes, and shape future behaviors. Guided by the central question of “how experiences are transformed into memories and how memories shape behaviors,” the laboratory investigates the formation, evolution, and functions of memory traces across multiple scales, spanning molecules, synapses, neuronal ensembles, neural circuits, and whole-brain networks. Beyond identifying the cellular and circuit substrates of memory, we aim to uncover how neuronal ensembles perform fundamental information-processing operations, including state inference, outcome prediction, experience association, and memory updating. By elucidating the computational principles underlying memory and behavior, we seek to understand how these processes promote experience integration, knowledge formation, and adaptive behaviors, providing insights into the neural basis of biological intelligence.

The laboratory employs diverse memory models, including emotional and threat memory, social memory, interoceptive memory, and motor and behavioral strategy memory, to investigate how new experiences are selectively incorporated into neuronal ensembles and how existing memories are retrieved, updated, or forgotten. We further examine how distinct memories are integrated through co-activation, offline replay, and cross-region coordination to generate neural representations that support generalization, rule learning, and concept formation, and how the brain leverages these representations to predict future outcomes, optimize behavioral strategies, and adapt to changing environments.

In disease-related research, the laboratory investigates brain disorders from the perspective of disrupted memory dynamics and impaired adaptive regulation, focusing on stress-related psychiatric disorders (e.g., anxiety, depression, and post-traumatic stress disorder), neurodevelopmental disorders associated with social dysfunction (e.g., autism spectrum disorder), and neurodegenerative disorders affecting cognition and movement. We aim to understand how maladaptive memories become persistently reinforced and abnormally generalized, why adaptive memories fail to form or be effectively retrieved to guide behavior, and how brain-body interactions, immune-metabolic signals, and interoceptive inputs reshape neuronal ensembles, circuit functions, and behavioral patterns over time. These studies seek to uncover the mechanisms underlying the emergence and progression of pathological brain states.

For translational applications, the laboratory explores memory principle–guided therapeutic strategies and investigates how pharmacological interventions, peripheral stimulation, and central neuromodulation induce long-lasting “therapeutic memory.” We aim to define the mechanisms governing the formation, stabilization, and reactivation of pro-recovery neuronal ensembles, and to develop approaches for selectively modifying pathological memories, restoring adaptive memory functions, and promoting neural circuit reconstruction. By integrating activity-dependent cell labeling, longitudinal neural activity tracking, closed-loop neuromodulation, and computational modeling, we seek to advance memory and brain disorder research from phenomenological observations toward mechanistic understanding, quantitative prediction, and precision intervention.

The major research directions include:

1. Deciphering the multiscale biological foundations and computational principles of memory traces

2. Elucidating how memory organization and abstraction support adaptive behaviors

3. Developing memory principle–inspired intervention strategies and translational applications