Deep brain stimulation of the olfactory bulb alleviates depressive-like behaviors and alters prefrontal cortex...

Treatment-resistant depression (TRD), marked by persistent depressive symptoms unresponsive to standard treatments, presents a significant challenge in psychiatry. Deep brain stimulation (DBS) has emerged as a novel intervention for TRD. This study examined the impact of DBS in the olfactory bulb (OB) on depressive symptoms, local field potentials (LFPs), and the medial prefrontal cortex (mPFC)-ventral hippocampus (vHPC) connectivity. Thirty-six male Wistar rats were assigned to four groups: control, chronic mild stress (CMS), CMS + DBS, and DBS. Stereotactic surgery was performed to implant electrodes in the OB, mPFC, and vHPC. The CMS protocol was administered for 3 weeks to induce depression. Behavioral assessments included the sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). During the final 4 days of CMS induction, the DBS groups received OB stimulation for one hour daily. On day 22, LFPs were recorded from the mPFC and vHPC and analyzed using MATLAB. Data were evaluated using ANOVA, with P-values ≤ 0.05 considered significant. Results indicated that three weeks of CMS reduced low-frequency gamma power in the mPFC and overall gamma power in the vHPC, along with decreased delta and theta band coherence between these regions. CMS also increased delta, theta, and alpha band power during exploration. OB-DBS improved depressive-like behaviors, enhanced low-frequency gamma power in both mPFC and vHPC, and increased delta and theta coherence. These findings suggest that depression's pathogenesis involves alterations in the mPFC-vHPC neural network, and that OB-DBS may counteract these changes, offering a potential therapeutic target for TRD.