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Nevertheless, the neural mechanisms underlying the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) remain poorly understood. In this study, we aimed to elucidate whether and how taVNS influences anxiety-like behaviors elicited by PTSD, focusing on synaptic plasticity in taVNS-activated neurons (TANs) of the anterior cingulate cortex (ACC). Our findings substantiate that taVNS significantly mitigates anxiety-like behaviors in PTSD-like male mice via activating specific glutamatergic neurons in the ACC. Notably, these glutamatergic TANs<jats:sup>ACC<\/jats:sup> exhibited marked enhancements in presynaptic excitatory transmission relative to those non-activated glutamatergic neurons in the ACC. This enhancement of presynaptic release further prevented the induction of presynaptic long-term potentiation (pre-LTP), manifesting as presynaptic depotentiation. Furthermore, inhibiting these glutamatergic TANs<jats:sup>ACC<\/jats:sup> weakened the positive effects of taVNS on anxiety-like behaviors in PTSD-like male mice. Conversely, activating these glutamatergic TANs<jats:sup>ACC<\/jats:sup> did not further amplify the effects of taVNS on anxiety-like behaviors. Collectively, our results reveal that the upregulation of presynaptic transmission in glutamatergic TANs<jats:sup>ACC<\/jats:sup> is responsible for the positive effects of taVNS on anxiety-like behaviors in PTSD-like male mice, providing new insights into functional and activity patterns of the specific brain regions involved in the effects of taVNS.<\/jats:p>","DOI":"10.1038\/s41398-025-03535-9","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T13:34:50Z","timestamp":1755956090000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Transcutaneous auricular vagus nerve stimulation alleviates anxiety-like behaviors in mice with post-traumatic stress disorder by regulating glutamatergic neurons in the anterior cingulate cortex"],"prefix":"10.1038","volume":"15","author":[{"given":"Zhijun","family":"Diao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-276X","authenticated-orcid":false,"given":"Jinming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-7426","authenticated-orcid":false,"given":"Haifa","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"3535_CR1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade5987","volume":"9","author":"KW Xi","year":"2023","unstructured":"Xi KW, Xiao HX, Huang X, Yuan ZD, Liu MY, Mao HH, et al. 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