Honors & Awards
MCHRI Postdoctoral Support Award, Maternal & Child Health Research Institute (2018-2020)
Doctor of Philosophy, Northeast Normal University (2014)
Lu Chen, Postdoctoral Faculty Sponsor
Defective memory engram reactivation underlies impaired fear memory recall in Fragile X syndrome.
Fragile X syndrome (FXS) is an X chromosome-linked disease associated with severe intellectual disabilities. Previous studies using the Fmr1 knockout (KO) mouse, an FXS mouse model, have attributed behavioral deficits to synaptic dysfunctions. However, how functional deficits at neural network level lead to abnormal behavioral learning remains unexplored. Here, we show that the efficacy of hippocampal engram reactivation is reduced in Fmr1 KO mice performing contextual fear memory recall. Experiencing an enriched environment (EE) prior to learning improved the engram reactivation efficacy and rescued memory recall in the Fmr1 KO mice. In addition, chemogenetically inhibiting EE-engaged neurons in CA1 reverses the rescue effect of EE on memory recall. Thus, our results suggest that inappropriate engram reactivation underlies cognitive deficits in FXS, and enriched environment may rescue cognitive deficits by improving network activation accuracy.
View details for DOI 10.7554/eLife.61882
View details for PubMedID 33215988
- 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 2019; 116 (14): 7113–22
Homeostatic synaptic plasticity as a metaplasticity mechanism-a molecular and cellular perspective.
Current opinion in neurobiology
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