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Science. 2019 Apr 12;364(6436). pii: eaat8078. doi: 10.1126/science.aat8078.

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

Author information

1
Brain and Mind Research Institute, Department of Psychiatry, and Sackler Institute for Developmental Psychobiology, Weill Cornell Medicine, New York, NY 10021, USA.
2
Departments of Bioengineering and of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
3
Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
4
Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
5
International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
6
Brain and Mind Research Institute, Department of Psychiatry, and Sackler Institute for Developmental Psychobiology, Weill Cornell Medicine, New York, NY 10021, USA. col2004@med.cornell.edu.
#
Contributed equally

Abstract

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.

PMID:
30975859
DOI:
10.1126/science.aat8078
[Indexed for MEDLINE]

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