Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation

The neurobiological mechanisms underlying the induction and remission of depressive episodes over time are not well understood. Through repeated longitudinal imaging of medial prefrontal microcircuits in the living brain, we found that prefrontal spinogenesis plays a critical role in sustaining specific antidepressant behavioral effects and maintaining long-term behavioral remission. Depression-related behavior was associated with targeted, branch-specific elimination of postsynaptic dendritic spines on prefrontal projection neurons. Antidepressant-dose ketamine reversed these effects by selectively rescuing eliminated spines and restoring coordinated activity in multicellular ensembles that predict motivated…

• NS
  National Science Foundation
• SF
  Simons Foundation

  Award: 429965
• WF
  Whitehall Foundation
• RA
  Rita Allen Foundation
• HF
  Hartwell Foundation
• JA
  Japan Agency for Medical Research and Development
• OM
  One Mind
• MO
  Ministry of Education, Culture, Sports, Science and Technology
• JS
  Japan Society for the Promotion of Science

  Award: Grant 17H06312
• NI
  National Institute of Mental Health

  Awards: R01 MH109685, R00 MH097822