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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pryazhnikov2018longitudinalscientific Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
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
DOI DOI not found
URL
http://link.springer.com/article/10.1038/s41598-018-24933-8
Keywords
Medicine (General) Medicine Science Medical emergencies. Critical care. Intensive care. First aid neurosciences. biological psychiatry. neuropsychiatry special situations and conditions communities. classes. races colonies and colonization. emigration and immigration. international migration

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