Related Experiment Video
Updated: Nov 4, 2025
Fear Incubation Using an Extended Fear-Conditioning Protocol for Rats
Published on: August 22, 2020
A multispecies probiotic accelerates fear extinction and inhibits relapse in mice: Role of microglia
Xiaoyu Cui1, Songhua Zhou1, Guang Xia2
1Department of Anesthesiology, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China; Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, 138th Tongzipo Road, Yuelu District, Changsha, 410013, People's Republic of China.
Abstract:
The relapse of fear memory remains a clinical challenge in treatment of fear-related disorders. Here we tested the effects and underlying mechanisms of probiotics treatment after fear conditioning on fear extinction. We found that fear conditioning induced synapse loss, microglial activation, and synaptic phagocytosis of activated microglial cells in hippocampal dentate gyrus of mice. And probiotics treatment (1 capsule/day/mice) after fear conditioning for 27 days inhibited these changes, promoted fear extinction, and inhibited the recovery of fear memory even 7 days after extinction. 16S rRNA gene sequencing demonstrated that probiotics supplement after fear conditioning partially normalized fear conditioning-induced dysbiosis of gut microbiota. In addition, we also found that repopulation of microglial cells in fear conditioning mice via PLX3397 treatment promoted long-term extinction of fear memory. Probiotics treatment after fear conditioning inhibited microglial activation and had similar therapeutic effects as the microglial cell repopulation induced by PLX3397 treatment. These data showed that (1) probiotics treatment after fear conditioning might promote long-term fear extinction which could be associated with the mitigation of synaptic pruning of activated microglial cells; (2) probiotics may be applicable as therapeutic strategy to inhibit microglial activation and treat fear-related disorders.
Insights
Probiotics treatment after fear conditioning mitigated synapse loss and microglial activation, promoting long-term fear extinction in mice. This suggests probiotics may offer a novel therapeutic strategy for fear-related disorders.
Area of Science:
- Neuroscience
- Microbiology
- Psychiatry
Background:
- Relapse of fear memory is a significant clinical challenge in treating fear-related disorders.
- Understanding the mechanisms underlying fear memory extinction is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the effects of probiotics on fear extinction after fear conditioning.
- To elucidate the underlying mechanisms, particularly the role of microglial activation and gut microbiota.
Main Methods:
- Fear conditioning and extinction paradigms in mice.
- Assessment of synaptic changes, microglial activation, and phagocytosis in the hippocampus.
- 16S rRNA gene sequencing to analyze gut microbiota composition.
- Pharmacological manipulation of microglial cells using PLX3397.
Main Results:
- Fear conditioning induced synapse loss and microglial activation in the hippocampus.
- Probiotics treatment inhibited these changes, promoted fear extinction, and prevented fear memory recovery.
- Probiotics partially normalized gut microbiota dysbiosis induced by fear conditioning.
- Microglial repopulation via PLX3397 treatment also promoted long-term fear extinction.
Conclusions:
- Probiotics treatment post-fear conditioning may promote long-term fear extinction by mitigating microglial-mediated synaptic pruning.
- Probiotics show potential as a therapeutic strategy for fear-related disorders by modulating microglial activation.
