Antidepressant-like Effects of Cortical Deep Brain Stimulation Coincide With Pro-neuroplastic Adaptations of Serotonin Systems
| Autor: | Jennifer Da, Sheryl G. Beck, Aseem Upadhyay, Collin Challis, Preetika Gupta, Olivier Berton, Avin Veerakumar |
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| Rok vydání: | 2014 |
| Předmět: |
Dorsal Raphe Nucleus
Male Deep brain stimulation Deep Brain Stimulation medicine.medical_treatment Ventromedial prefrontal cortex Prefrontal Cortex Mice Transgenic Inhibitory postsynaptic potential Social defeat Mice Dorsal raphe nucleus Neuroplasticity medicine Animals Prefrontal cortex Biological Psychiatry Depression Dentate gyrus Brain Adaptation Physiological Mice Inbred C57BL medicine.anatomical_structure Inhibitory Postsynaptic Potentials nervous system Psychology Neuroscience Serotonergic Neurons |
| Zdroj: | Biological Psychiatry. 76:203-212 |
| ISSN: | 0006-3223 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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