Longitudinal two-photon imaging in somatosensory cortex of behaving mice reveals dendritic spine formation enhancement by subchronic administration of low-dose ketamine
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2018
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Abstract
Abstract Ketamine, a well-known anesthetic, has recently attracted renewed attention as a fast-acting antidepressant. A single dose of ketamine induces rapid synaptogenesis, which may underlie its antidepressant effect. To test whether repeated exposure to ketamine triggers sustained synaptogenesis, we administered a sub-anesthetic dose of ketamine (10 mg/kg i.p.) once-daily for 5 days, and repeatedly imaged dendritic spines of the YFP-expressing pyramidal neurons in somatosensory cortex of awake female mice using in vivo two-photon microscopy. We found that the spine formation rate became significantly higher at 72–132 h after the first ketamine injection (but not at 6–24 h), while the rate of elimination of pre-existing spines remained unchanged. In contrast to the net gain of spines observed in ketamine-treated mice, the vehicle-injected control mice exhibited a net loss typical for young-adult animals undergoing synapse pruning. Ketamine-induced spinogenesis was correlated with increased PSD-95 and phosphorylated actin, consistent with formation of new synapses. Moreover, structural synaptic plasticity caused by ketamine was paralleled by a significant improvement in the nest building behavioral assay. Taken together, our data show that subchronic low-dose ketamine induces a sustained shift towards spine formation.
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| Authors | Pryazhnikov, Evgeny;Mugantseva, Ekaterina;Casarotto, Plinio;Kolikova, Julia;Fred, Senem Merve;Toptunov, Dmytro;Afzalov, Ramil;Hotulainen, Pirta;Voikar, Vootele;Terry-Lorenzo, Ryan;Engel, Sharon;Kirov, Sergei;Castren, Eero;Khiroug, Leonard; |
| Journal | Scientific reports |
| Year | 2018 |
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