Deep brain stimulation ameliorates social deficits from early-life pain by restoring excitatory/inhibitory balance in the anterior cingulate cortex
- 1Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053 China
Abstract
The neural mechanisms underlying how early-life pain leads to long-term impairments in adult social deficit remain largely elusive. Here, by establishing a juvenile inflammatory pain model in mice and employing a combination of neuromodulation techniques, we found that early-life pain experience induces a specific and enduring social deficit in adulthood. This deficit originates from a persistent excitatory/inhibitory (E/I) imbalance within the anterior cingulate cortex (ACC). Specifically, during social interaction, we observed diminished activity in ACC excitatory neurons alongside hyperfunction of inhibitory GABAergic neurons, resulting in insufficient synaptic glutamate release. Targeted metabolomics analysis further confirmed aberrant levels of glutamate and GABA within the ACC. Targeting this mechanism, we demonstrated that either enhancing ACC excitation or dampening its inhibition via optogenetic and chemogenetic manipulations effectively rescued the social deficit. Importantly, deep brain stimulation (DBS) targeting the ACC also activated excitatory neurons and successfully reversed this social deficit. This study unveils a core mechanism whereby early-life pain impairs social function by inducing a state of hypoexcitation and hyperinhibition in the ACC. Furthermore, we establish that DBS can effectively rectify this ACC imbalance, providing a novel theoretical basis and a potential translational strategy for intervening in social deficits associated with developmental trauma.
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BibTeX
@article{wan2026deep,
title = {{Deep brain stimulation ameliorates social deficits from early-life pain by restoring excitatory/inhibitory balance in the anterior cingulate cortex}},
author = {Xiangdong Wan and Tao Du and Dou Yang and Zaiying Jiang and Xiangyu Zhang and Yunjian Huang and Siyi Liu and Shiyun Xu and He Zhang and Guang Lu and Bing Ni and Hongwei Zhu},
journal = {Translational Psychiatry},
year = {2026},
month = jul,
doi = {10.1038/s41398-026-04311-z},
url = {https://doi.org/10.1038/s41398-026-04311-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Deep brain stimulation ameliorates social deficits from early-life pain by restoring excitatory/inhibitory balance in the anterior cingulate cortex
AU - Xiangdong Wan
AU - Tao Du
AU - Dou Yang
AU - Zaiying Jiang
AU - Xiangyu Zhang
AU - Yunjian Huang
AU - Siyi Liu
AU - Shiyun Xu
AU - He Zhang
AU - Guang Lu
AU - Bing Ni
AU - Hongwei Zhu
PY - 2026
DA - 2026/07/30
JO - Translational Psychiatry
DO - 10.1038/s41398-026-04311-z
UR - https://doi.org/10.1038/s41398-026-04311-z
AB - The neural mechanisms underlying how early-life pain leads to long-term impairments in adult social deficit remain largely elusive. Here, by establishing a juvenile inflammatory pain model in mice and employing a combination of neuromodulation techniques, we found that early-life pain experience induces a specific and enduring social deficit in adulthood. This deficit originates from a persistent excitatory/inhibitory (E/I) imbalance within the anterior cingulate cortex (ACC). Specifically, during social interaction, we observed diminished activity in ACC excitatory neurons alongside hyperfunction of inhibitory GABAergic neurons, resulting in insufficient synaptic glutamate release. Targeted metabolomics analysis further confirmed aberrant levels of glutamate and GABA within the ACC. Targeting this mechanism, we demonstrated that either enhancing ACC excitation or dampening its inhibition via optogenetic and chemogenetic manipulations effectively rescued the social deficit. Importantly, deep brain stimulation (DBS) targeting the ACC also activated excitatory neurons and successfully reversed this social deficit. This study unveils a core mechanism whereby early-life pain impairs social function by inducing a state of hypoexcitation and hyperinhibition in the ACC. Furthermore, we establish that DBS can effectively rectify this ACC imbalance, providing a novel theoretical basis and a potential translational strategy for intervening in social deficits associated with developmental trauma.
SN - 2158-3188
ER -