Abstract
Recent studies have shown that ELA disrupts conditional fear behavior in mice; however, whether ELA affects innate fear behavior remains largely unknown. Here, we report that ELA induced by social deprivation on postnatal days 10–20 impairs looming-evoked innate defensive behaviors via an oxytocin (OT) signaling deficit. ELA leads to decreased OT receptor mRNA levels in the intermediate and deep layers of the superior colliculus (IDSC), and knockdown of this receptor in the superior colliculus mimics the defensive behavior deficit induced by ELA. OT neurons in the paraventricular nucleus of the hypothalamus modulate looming-evoked innate defensive behavior through projections to the IDSC. Moreover, intranasal OT ameliorated ELA-induced deficits in defensive behavior. This study provides a theoretical basis for understanding how ELA induces a fear processing deficit that contributes to psychopathological outcomes and represents an initial step toward identifying potential treatment strategies.
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Acknowledgements
We would like to thank Prof. Xiang Yu (School of Life Sciences, Peking University) for providing the OT-Cre (Jackson Laboratory) and Oxtrflox mice (Jackson Laboratory). This work was supported by the National Key R&D Program of China 2022YFE0140400 (to Qingqing Liu), the National Natural Science Foundation of China (32230042 to Liping Wang and 32200828 to Shanping Chen), Financial Support for Outstanding Talents Training Fund in Shenzhen (to Liping Wang), GuangDong Basic and Applied Basic Research Foundation 2023A1515111193 (to Huiying Tan), the CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024), and Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2023B1212060055). We sincerely thank the Shenzhen Brain Science Infrastructure for their essential technical support in this study.
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Liping Wang and Huiying Tan designed the study and the experiments. Huiying Tan, Junying Su, and Shaohua Ma performed the experiments. Shanping Chen analyzed the data. Huiying Tan drafted the manuscript. Qingqing Liu and Xing Yang commented on the manuscript. Liping Wang supervised all aspects of this study.
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Tan, H., Su, J., Ma, S. et al. Early life adversity impairs visually evoked innate defensive behaviors via oxytocin signaling. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09738-0
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DOI: https://doi.org/10.1038/s42003-026-09738-0
