Honors & Awards

  • MCHRI Postdoctoral Support Award, Maternal & Child Health Research Institute (2018)

Professional Education

  • Doctor of Philosophy, Northeast Normal University (2014)

Stanford Advisors

  • Lu Chen, Postdoctoral Faculty Sponsor

All Publications

  • Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning. Proceedings of the National Academy of Sciences of the United States of America Hsu, Y., Li, J., Wu, D., Sudhof, T. C., Chen, L. 2019


    Homeostatic synaptic plasticity is a stabilizing mechanism engaged by neural circuits in response to prolonged perturbation of network activity. The non-Hebbian nature of homeostatic synaptic plasticity is thought to contribute to network stability by preventing "runaway" Hebbian plasticity at individual synapses. However, whether blocking homeostatic synaptic plasticity indeed induces runaway Hebbian plasticity in an intact neural circuit has not been explored. Furthermore, how compromised homeostatic synaptic plasticity impacts animal learning remains unclear. Here, we show in mice that the experience of an enriched environment (EE) engaged homeostatic synaptic plasticity in hippocampal circuits, thereby reducing excitatory synaptic transmission. This process required RARalpha, a nuclear retinoic acid receptor that doubles as a cytoplasmic retinoic acid-induced postsynaptic regulator of protein synthesis. Blocking RARalpha-dependent homeostatic synaptic plasticity during an EE experience by ablating RARalpha signaling induced runaway Hebbian plasticity, as evidenced by greatly enhanced long-term potentiation (LTP). As a consequence, RARalpha deletion in hippocampal circuits during an EE experience resulted in enhanced spatial learning but suppressed learning flexibility. In the absence of RARalpha, moreover, EE experience superactivated mammalian target of rapamycin (mTOR) signaling, causing a shift in protein translation that enhanced the expression levels of AMPA-type glutamate receptors. Treatment of mice with the mTOR inhibitor rapamycin during an EE experience not only restored normal AMPA-receptor expression levels but also reversed the increases in runaway Hebbian plasticity and learning after hippocampal RARalpha deletion. Thus, our findings reveal an RARalpha- and mTOR-dependent mechanism by which homeostatic plasticity controls Hebbian plasticity and learning.

    View details for PubMedID 30782829

  • Homeostatic synaptic plasticity as a metaplasticity mechanism-a molecular and cellular perspective. Current opinion in neurobiology Li, J., Park, E., Zhong, L. R., Chen, L. 2018; 54: 44–53


    The molecular mechanisms underlying various types of synaptic plasticity are historically regarded as separate processes involved in independent cellular events. However, recent progress in our molecular understanding of Hebbian and homeostatic synaptic plasticity supports the observation that these two types of plasticity share common cellular events, and are often altered together in neurological diseases. Here, we discuss the emerging concept of homeostatic synaptic plasticity as a metaplasticity mechanism with a focus on cellular signaling processes that enable a direct interaction between Hebbian and homeostatic plasticity. We also identify distinct and shared molecular players involved in these cellular processes that may be explored experimentally in future studies to test the hypothesis that homeostatic synaptic plasticity serves as a metaplasticity mechanism to integrate changes in neuronal activity and support optimal Hebbian learning.

    View details for PubMedID 30212714