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Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

Nature medicine | 2018

Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

Pubmed ID: 29662202 RIS Download

Associated grants

  • Agency: NIH HHS, United States
    Id: S10 OD021630
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH113262
  • Agency: NIDA NIH HHS, United States
    Id: R21 DA023701
  • Agency: NIDA NIH HHS, United States
    Id: T32 DA007290
  • Agency: NIMH NIH HHS, United States
    Id: T32 MH076690
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH104471
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH106511
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS059934
  • Agency: NICHD NIH HHS, United States
    Id: U54 HD086984
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH107945
  • Agency: NIDA NIH HHS, United States
    Id: K02 DA023555

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