Propofol Modulates Fear Memory Reconsolidation by Inhibiting D2 Receptor-Expressing Neurons in the Medial Prefrontal Cortex.
5 affiliations
- 1Shanghai Key Laboratory of Mental Disorders Translational Research, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine and School of Psychology, Shanghai, China.
- 2School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
- 3Department of Psychiatry, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
- 4Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 5Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
Fear memory reconsolidation provides a temporal window for modifying established fear memories, yet the underlying cellular and neural circuit mechanisms remain incompletely understood. Using in vivo fiber photometry and chemogenetic approaches in freely moving mice, we show that propofol modulates fear memory reconsolidation by inhibiting D2 receptor-expressing neurons in the medial prefrontal cortex (mPFC). These neurons exhibit heightened activity during fear memory reconsolidation and project prominently to the basolateral amygdala (BLA). Notably, local pharmacological activation of D2 receptors in the mPFC recapitulates the fear-attenuating effect of propofol when administered during the reconsolidation window. Circuit-level investigations further show that propofol suppresses the reconsolidation-associated enhancement of the mPFCD2-BLA synaptic transmission, and chemogenetic activation of this projection counteracts the effect of propofol on fear memory reconsolidation. Moreover, selective knockdown of D2 receptors in BLA-projecting mPFC neurons diminishes the effect of propofol, supporting a critical role for D2 receptor signaling within this projection-defined circuit. Together, these findings identify the mPFCD2-BLA circuit as a key neural substrate through which propofol modulates fear memory reconsolidation and highlight prefrontal D2 receptor signaling as a potential target for reconsolidation-based interventions aimed at maladaptive fear memories.
Related
- Inhibiting the right dorsolateral prefrontal cortex selectively enhances unsupervised statistical learning
- Adenoviral vector co-expressing ALDH1 and ADH1 mitigates alcohol toxicity and modulates glucose and lipid metabolism
- Face your fears: attenuating remote fear memories by reconsolidation-updating
- Aging disrupts transcriptional programs for memory updating in the dorsal hippocampus and reveals a required role for Tent5a in reconsolidation
- Auricular vagus nerve stimulation facilitates contextual fear extinction via insular-mPFC pathway without affecting reconsolidation
BibTeX
@article{li2026propofol,
title = {{Propofol Modulates Fear Memory Reconsolidation by Inhibiting D2 Receptor-Expressing Neurons in the Medial Prefrontal Cortex.}},
author = {Jie Li and Yi-Ge Guo and Xing Xu and Gui-Lin Meng and Han Li and Liu-Wei Chu and Xin-Yuan Chen and Xiao-Yun Guo and Tao Xu and Ti-Fei Yuan and Ji Hu and Xiao-Na Zhu},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78527},
url = {https://europepmc.org/article/MED/42952178},
note = {CC BY},
}
RIS
TY - JOUR
TI - Propofol Modulates Fear Memory Reconsolidation by Inhibiting D2 Receptor-Expressing Neurons in the Medial Prefrontal Cortex.
AU - Jie Li
AU - Yi-Ge Guo
AU - Xing Xu
AU - Gui-Lin Meng
AU - Han Li
AU - Liu-Wei Chu
AU - Xin-Yuan Chen
AU - Xiao-Yun Guo
AU - Tao Xu
AU - Ti-Fei Yuan
AU - Ji Hu
AU - Xiao-Na Zhu
PY - 2026
DA - 2026/10/28
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78527
UR - https://europepmc.org/article/MED/42952178
AB - Fear memory reconsolidation provides a temporal window for modifying established fear memories, yet the underlying cellular and neural circuit mechanisms remain incompletely understood. Using in vivo fiber photometry and chemogenetic approaches in freely moving mice, we show that propofol modulates fear memory reconsolidation by inhibiting D2 receptor-expressing neurons in the medial prefrontal cortex (mPFC). These neurons exhibit heightened activity during fear memory reconsolidation and project prominently to the basolateral amygdala (BLA). Notably, local pharmacological activation of D2 receptors in the mPFC recapitulates the fear-attenuating effect of propofol when administered during the reconsolidation window. Circuit-level investigations further show that propofol suppresses the reconsolidation-associated enhancement of the mPFCD2-BLA synaptic transmission, and chemogenetic activation of this projection counteracts the effect of propofol on fear memory reconsolidation. Moreover, selective knockdown of D2 receptors in BLA-projecting mPFC neurons diminishes the effect of propofol, supporting a critical role for D2 receptor signaling within this projection-defined circuit. Together, these findings identify the mPFCD2-BLA circuit as a key neural substrate through which propofol modulates fear memory reconsolidation and highlight prefrontal D2 receptor signaling as a potential target for reconsolidation-based interventions aimed at maladaptive fear memories.
SN - 2198-3844
ER -