{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kim TE"],"funding":["National Research Foundation of Korea","National Research Foundation","Korea Brain Research Institute"],"pagination":["100320"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907709"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["49(3)"],"pubmed_abstract":["Stress-related psychiatric disorders are underpinned by dysfunction in the prefrontal cortex and hippocampus; however, the underlying circuit-specific mechanisms remain ill-defined. Here, we identified the basolateral amygdala (BLA)-to-ventral hippocampus (vHPC) circuit as a critical regulator of stress-coping behaviors. Although chronic social defeat stress reduced the mGluR5 expression in both the vHPC and medial prefrontal cortex (mPFC), our circuit-specific behavioral analysis revealed that the activation of the BLA-vHPC circuit produced a significantly greater improvement in coping behavior compared with the activation of the BLA-mPFC circuit. Subsequently, we mechanistically demonstrated that reduced mGluR5 in the vHPC directly impairs CREB-mediated brain-derived neurotrophic factor (BDNF) transcription, a molecular cascade tightly linked to passive coping. These findings reveal a novel circuit-specific molecular mechanism governing stress recovery, positioning the mGluR5-BDNF pathway as a highly specific and promising therapeutic target for future gene therapy interventions."],"journal":["Molecules and cells"],"pubmed_title":["Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling."],"pmcid":["PMC12907709"],"funding_grant_id":["26-BR-05-02","RS-2024-000460958","2021R1A2C2094627"],"pubmed_authors":["Choi TY","Kim TE","Koo JW","Kim J"],"additional_accession":[]},"is_claimable":false,"name":"Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling.","description":"Stress-related psychiatric disorders are underpinned by dysfunction in the prefrontal cortex and hippocampus; however, the underlying circuit-specific mechanisms remain ill-defined. Here, we identified the basolateral amygdala (BLA)-to-ventral hippocampus (vHPC) circuit as a critical regulator of stress-coping behaviors. Although chronic social defeat stress reduced the mGluR5 expression in both the vHPC and medial prefrontal cortex (mPFC), our circuit-specific behavioral analysis revealed that the activation of the BLA-vHPC circuit produced a significantly greater improvement in coping behavior compared with the activation of the BLA-mPFC circuit. Subsequently, we mechanistically demonstrated that reduced mGluR5 in the vHPC directly impairs CREB-mediated brain-derived neurotrophic factor (BDNF) transcription, a molecular cascade tightly linked to passive coping. These findings reveal a novel circuit-specific molecular mechanism governing stress recovery, positioning the mGluR5-BDNF pathway as a highly specific and promising therapeutic target for future gene therapy interventions.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-07-06T03:18:20.57Z","creation":"2026-07-06T03:11:44.399Z"},"accession":"S-EPMC12907709","cross_references":{"pubmed":["41577137"],"doi":["10.1016/j.mocell.2026.100320"]}}