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

TitleSustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation.
Publication TypeJournal Article
Year of Publication2019
AuthorsModa-Sava RN, Murdock MH, Parekh PK, Fetcho RN, Huang BS, Huynh TN, Witztum J, Shaver DC, Rosenthal DL, Alway EJ, Lopez K, Meng Y, Nellissen L, Grosenick L, Milner TA, Deisseroth K, Bito H, Kasai H, Liston C
JournalScience
Volume364
Issue6436
Date Published2019 04 12
ISSN1095-9203
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.

DOI10.1126/science.aat8078
Alternate JournalScience
PubMed ID30975859
Grant ListR00 MH097822 / MH / NIMH NIH HHS / United States
R01 MH109685 / MH / NIMH NIH HHS / United States
R01 MH118451 / MH / NIMH NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
F30 MH115622 / MH / NIMH NIH HHS / United States
R01 DA008259 / DA / NIDA NIH HHS / United States
R01 HL136520 / HL / NHLBI NIH HHS / United States