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Updated: Oct 12, 2026

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation
Published on: July 16, 2014
Antidepressant-like effects of cortical deep brain stimulation coincide with pro-neuroplastic adaptations of
Avin Veerakumar1, Collin Challis2, Preetika Gupta2
1Department of Psychiatry, Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
Background:
Cortical deep brain stimulation (DBS) is a promising therapeutic option for treatment-refractory depression, but its mode of action remains enigmatic. Serotonin (5-HT) systems are engaged indirectly by ventromedial prefrontal cortex (vmPFC) DBS. Resulting neuroplastic changes in 5-HT systems could thus coincide with the long-term therapeutic activity of vmPFC DBS.
Methods:
We tested this hypothesis by evaluating the antidepressant-like activity of vmPFC DBS in the chronic social defeat stress (CSDS) model of depression (n = 8-13 mice/group). Circuit-wide activation induced by vmPFC DBS was mapped with c-Fos immunolabeling. The effects of chronic vmPFC DBS on the physiology and morphology of genetically identified 5-HT cells from the dorsal raphe nucleus (DRN) were examined with whole-cell recording, somatodendritic three-dimensional reconstructions and morphometric analyses of presynaptic boutons along 5-HT axons.
Results:
Acute DBS drove c-Fos expression locally in the vmPFC and in several distal monosynaptically connected regions, including the DRN. Chronic DBS reversed CSDS-induced social avoidance, restored the disrupted balance of excitatory/inhibitory inputs onto 5-HT neurons, and reversed 5-HT hypoexcitability observed after CSDS. Furthermore, vmPFC DBS reversed CSDS-induced arborization of 5-HT dendrites in the DRN and increased the size and density of 5-HT presynaptic terminals in the dentate gyrus and vmPFC.
Conclusions:
We validate a new preclinical paradigm to examine cellular mechanisms underlying the antidepressant-like activity of vmPFC DBS and identify dramatic circuit-mediated cellular adaptations that coincide with this treatment. These neuroplastic changes of 5-HT neurons might contribute to the progressive mood improvements reported in patients treated with chronic courses of cortical DBS.
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