Longitudinal two-photon imaging in somatosensory cortex of behaving mice reveals dendritic spine formation enhancement by subchronic administration of low-dose ketamine

Evgeny Pryazhnikov, Ekaterina Mugantseva, Plinio Casarotto, Julia Kolikova, Senem Merve Fred, Dmytro Toptunov, Ramil Afzalov, Pirta Hotulainen, Vootele Voikar, Ryan Terry-Lorenzo, Sharon Engel, Sergei A Kirov, Eero Castren, Leonard Khiroug

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number6464
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Dendritic Spines
Somatosensory Cortex
Ketamine
Photons
Spine
Synapses
Antidepressive Agents
Anesthetics
Neuronal Plasticity
Pyramidal Cells
Actins
Young Adult
Microscopy
Injections

ASJC Scopus subject areas

  • General

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Longitudinal two-photon imaging in somatosensory cortex of behaving mice reveals dendritic spine formation enhancement by subchronic administration of low-dose ketamine. / 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 A; Castren, Eero; Khiroug, Leonard.

In: Scientific Reports, Vol. 8, No. 1, 6464, 01.12.2018.

Research output: Contribution to journalArticle

Pryazhnikov, E, Mugantseva, E, Casarotto, P, Kolikova, J, Fred, SM, Toptunov, D, Afzalov, R, Hotulainen, P, Voikar, V, Terry-Lorenzo, R, Engel, S, Kirov, SA, Castren, E & Khiroug, L 2018, 'Longitudinal two-photon imaging in somatosensory cortex of behaving mice reveals dendritic spine formation enhancement by subchronic administration of low-dose ketamine', Scientific Reports, vol. 8, no. 1, 6464. https://doi.org/10.1038/s41598-018-24933-8
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 A ; Castren, Eero ; Khiroug, Leonard. / Longitudinal two-photon imaging in somatosensory cortex of behaving mice reveals dendritic spine formation enhancement by subchronic administration of low-dose ketamine. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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