C1ql2 gates stress vulnerability by regulating microglia-mediated synaptic pruning in the BLA-vHPC circuit
5 affiliations
- 1Jiangxi Institute of Respiratory Diseases and Department of Pathology, The First Affiliated Hospital, School of Basic Medical Sciences and Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
- 2Jiangxi Provincial Key Laboratory of Brain Science and Brain Health, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
- 3Postdoctoral Research Station, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
- 4Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
- 5Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
Abstract
Synaptic remodeling in emotional circuits contributes to the development of stress-related emotional disorders. However, such remodeling generally exhibits considerable heterogeneity across specific neuronal populations and the underlying molecular mechanisms remain poorly understood. Here, we identified C1ql2 as a key molecular regulator that governs projection-specific synaptic vulnerability within basolateral amygdala (BLA). Transcriptional profiling revealed that C1ql2 expression is enriched in BLA neurons projecting to ventral hippocampus (BLA→vHPC PNs), but not in those projecting to nucleus accumbens (NAc), and is significantly down-regulated following chronic social defeat stress (CSDS). Gain- and loss-of-function manipulations demonstrated that C1ql2 regulates stress-induced neuronal remodeling in BLA→vHPC PNs, including dendritic hypertrophy, synaptic outgrowth, and enhanced glutamatergic transmission, thereby shaping susceptibility to anxiety-like behavior. We further found that CSDS-induced C1ql2 loss impairs microglial engulfment of BLA→vHPC PNs synapses, leading to aberrant synaptic accumulation. Our findings establish C1ql2-mediated neuron-microglia cross talk that critically regulates circuit-specific synaptic pathophysiology in stress-related disorders.
Related
- Dendrimer Delivered shRNA Targeting the CCL20-CCR6 Axis Suppresses Complement-Mediated Microglial Synaptic Pruning and Ameliorates Chronic Neuroinflammation After Repetitive Traumatic Brain Injury
- Excessive cholesterol accumulation in microglia increases neuronal synaptic vulnerability to amyloid-beta
- A physiological Na+ signal activates mitochondrial PINK1 to couple synaptic depression to caspase-3-dependent spine pruning
- Magel2 deficiency drives microglial synaptic engulfment and alters neuron-microglia interactions in Prader-Willi syndrome
- LATS2 modulates synaptic organization and function by regulating actin dynamics
BibTeX
@article{wang2026c1ql2,
title = {{C1ql2 gates stress vulnerability by regulating microglia-mediated synaptic pruning in the BLA-vHPC circuit}},
author = {Chun-Yan Wang and Wei-Zhu Liu and Shuang-Mei Liao and Jing Niu and Han-Qing Pan and Wen-Jie You and Ke Zhao and Bao Ma and Ming-Fen Lu and Jia-Xin Zou and Ping Hu and Wen-Hua Zhang and Bing-Xing Pan},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2600854123},
url = {https://doi.org/10.1073/pnas.2600854123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - C1ql2 gates stress vulnerability by regulating microglia-mediated synaptic pruning in the BLA-vHPC circuit
AU - Chun-Yan Wang
AU - Wei-Zhu Liu
AU - Shuang-Mei Liao
AU - Jing Niu
AU - Han-Qing Pan
AU - Wen-Jie You
AU - Ke Zhao
AU - Bao Ma
AU - Ming-Fen Lu
AU - Jia-Xin Zou
AU - Ping Hu
AU - Wen-Hua Zhang
AU - Bing-Xing Pan
PY - 2026
DA - 2026/10/21
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2600854123
UR - https://doi.org/10.1073/pnas.2600854123
AB - Synaptic remodeling in emotional circuits contributes to the development of stress-related emotional disorders. However, such remodeling generally exhibits considerable heterogeneity across specific neuronal populations and the underlying molecular mechanisms remain poorly understood. Here, we identified C1ql2 as a key molecular regulator that governs projection-specific synaptic vulnerability within basolateral amygdala (BLA). Transcriptional profiling revealed that C1ql2 expression is enriched in BLA neurons projecting to ventral hippocampus (BLA→vHPC PNs), but not in those projecting to nucleus accumbens (NAc), and is significantly down-regulated following chronic social defeat stress (CSDS). Gain- and loss-of-function manipulations demonstrated that C1ql2 regulates stress-induced neuronal remodeling in BLA→vHPC PNs, including dendritic hypertrophy, synaptic outgrowth, and enhanced glutamatergic transmission, thereby shaping susceptibility to anxiety-like behavior. We further found that CSDS-induced C1ql2 loss impairs microglial engulfment of BLA→vHPC PNs synapses, leading to aberrant synaptic accumulation. Our findings establish C1ql2-mediated neuron-microglia cross talk that critically regulates circuit-specific synaptic pathophysiology in stress-related disorders.
SN - 0027-8424
SN - 1091-6490
ER -