Longitudinal Effects of Ketamine on Dendritic ArchitectureIn Vivoin the Mouse Medial Frontal Cortex
Victoria Phoumthipphavong, Florent Barthas, Samantha Hassett, Alex C. Kwan
eNeuro March 1, 2016 DOI: 10.1523/eneuro.0133-15.2016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Longitudinal Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | Ketamine |
| Dose | single subanesthetic dose |
| Duration | Up to 2 weeks |
| Topics | Ketamine Esketamine |
| Keywords | Dendritic spine Hippocampus Nmda receptor In vivo Prefrontal cortex Cortex anatomy Hippocampal formation |
| Citations | 142 |
| Key findings | A single systemic ketamine injection in mice increased dendritic spine density in the medial frontal cortex for up to two weeks, driven by elevated spine formation rate. |
Abstract
A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 57
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
- Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines Nature Communications June 3, 2019
and 52 more in the library
Cites 7
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions Proceedings of the National Academy of Sciences June 8, 2015
- Imaging patients with psychosis and a mouse model establishes a spreading pattern of hippocampal dysfunction and implicates glutamate as a pathogenic driver Neuron April 10, 2013
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
and 2 more in the library