{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:31:23Z","timestamp":1789007483677,"version":"build-2803163510"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>Deep brain stimulation of the nucleus accumbens (NAc-DBS) has been shown to ameliorate depressive-like behaviors. However, the underlying mechanisms of action remain elusive. We aimed to investigate the impact of NAc-DBS on synaptic spine alterations in hippocampus in a depression mice model and unveil the possible signal pathway mediating such effects. The experimental protocol involved exposing adult mice to chronic unpredictable mild stress (CUMS) with or without NAc-DBS. Behavioral assessments were performed to evaluate the impact of NAc-DBS on emotional alterations. Local field potential (LFP) recordings were employed to examine the hippocampal neuronal activity in awake mice. Golgi-Cox staining was applied to quantify modifications in dendritic spine density. Additionally, hippocampal protein expression of postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and the protein kinase B (AKT)\/mammalian target of rapamycin (mTOR) signaling pathway were analyzed. Results indicate that CUMS mice exhibited apparent depressive-like behaviors, concomitant with reduced hippocampal high gamma oscillation power and synaptic spine density. In addition, CUMS reduced the expression level of PSD-95 and BDNF in mice hippocampus, as well as phosphorylated AKT and mTOR protein. The study revealed that NAc-DBS could attenuate depression-like behaviors, restore high gamma oscillation power and enhance synaptic spine density, potentially by increasing BDNF protein expression level and activating AKT\/mTOR signaling pathway. Furthermore, Rapamycin, a potent and specific mTOR inhibitor, was found to moderate the effects of NAc-DBS. These findings suggest that NAc-DBS could enhance synaptic spine density via AKT\/mTOR\/BDNF signal pathway, which may partially underline its potential antidepressant effects in CUMS induced depressive models.<\/jats:p>","DOI":"10.3389\/fnbeh.2025.1662449","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:53:48Z","timestamp":1761720828000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["AKT\/mTOR\/BDNF pathway mediates the antidepressant-like effects of NAc-DBS in a mouse model of depression"],"prefix":"10.3389","volume":"19","author":[{"given":"Ranran","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongtao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujing","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangping","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.lfs.2014.02.014","article-title":"The role of mTOR in depression and antidepressant responses","volume":"101","author":"Abelaira","year":"2014","journal-title":"Life Sci."},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/srep31613","article-title":"Functional magnetic resonance imaging of electrical and Optogenetic deep brain stimulation at the rat nucleus Accumbens","volume":"6","author":"Albaugh","year":"2016","journal-title":"Sci. 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