Archival ReportAntidepressant-like Effects of Cortical Deep Brain Stimulation Coincide With Pro-neuroplastic Adaptations of Serotonin Systems
Section snippets
Animals
Eight- to twelve-week-old male wild-type (for behavior and c-Fos experiments) or Pet1-tdTomato transgenic mice (for electrophysiology and morphology experiments) bred onto a C57BL/6 background were used for all experiments (generation of transgenic mice is described in Supplement 1). Mice were housed on a 12-hour light/dark cycle with food and water available ad libitum, except during DBS or sham stimulation. All studies were conducted strictly according to protocols approved by the University
Antidepressant-Like Effect of Chronic vmPFC DBS in Stress-Susceptible Mice
We first investigated the behavioral effect of chronic vmPFC DBS in the CSDS paradigm (Figure 1A). Histological analyses confirmed that DBS electrodes were placed in the vmPFC during experiments (Figure 1B). A social interaction test conducted on Day 11 before surgery verified that interaction times were decreased in defeat-susceptible mice (main effect of defeat F1,36 = 167.11, p = 4.33 × 10−15) (Figure 1C, left). When social interaction was retested on Day 25 after 7 days of chronic vmPFC
Discussion
In this study we have demonstrated that chronic vmPFC DBS reverses social avoidance in a mouse model of depression and induces striking neuroadaptations in brainstem 5-HT neurons that reverse CSDS-induced maladaptive plasticity and point to a sustained increase in 5-HT activity upon repeated courses of DBS.
We first built on previous studies of cortical DBS in the chronic mild stress model 7, 31 by demonstrating the efficacy of DBS in modulating CSDS-induced social avoidance, which models
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