Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation Academic Article Article uri icon


MeSH Major

  • B-Lymphocytes
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Pre-B Cell Receptors
  • Precursor Cells, B-Lymphoid


  • © 2019 American Association for the Advancement of Science. All rights reserved. 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 escape behavior. Prefrontal spinogenesis was required for the long-term maintenance of antidepressant effects on motivated escape behavior but not for their initial induction.

publication date

  • April 12, 2019



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1126/science.aat8078

PubMed ID

  • 30975859

Additional Document Info


  • 364


  • 6436