Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • A Etiévant
  • ,
  • C Oosterhof, Denmark
  • C Bétry
  • ,
  • E Abrial, Denmark
  • M Novo-Perez, Denmark
  • R Rovera, Denmark
  • H Scarna, Denmark
  • C Devader, Denmark
  • J Mazella
  • ,
  • G Wegener
  • C Sánchez
  • O Dkhissi-Benyahya, Denmark
  • C Gronfier, Denmark
  • V Coizet, Denmark
  • J M Beaulieu
  • ,
  • P Blier
  • ,
  • G Lucas
  • ,
  • N Haddjeri

Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

Original languageEnglish
JournalEBioMedicine
Volume2
Issue8
Pages (from-to)896-906
Number of pages11
DOIs
Publication statusPublished - Aug 2015

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