Related Experiment Video
Updated: Aug 5, 2026
10:30
Prolonged Incubation of Acute Neuronal Tissue for Electrophysiology and Calcium-imaging
Published on: February 15, 2017
Ketamine persists within neuronal compartments long after systemic clearance
Research Square
|August 1, 2026
Summary
Ketamine
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Ketamine's rapid antidepressant effects are well-documented.
- The precise cellular and subcellular distribution of ketamine remains largely unknown.
- Intracellular accumulation in acidic compartments is hypothesized.
Purpose of the Study:
- To develop tools for visualizing ketamine's distribution and engagement in neurons.
- To investigate ketamine's intracellular dynamics and subcellular localization.
- To link ketamine's intracellular persistence to its behavioral effects.
Main Methods:
- Development of genetically encoded ketamine-sensing fluorescent reporters (iKetSnFRs).
- In vitro and in vivo imaging of ketamine distribution in mouse brain.
- Engineering of compartment-targeted iKetSnFR variants for organelle-specific tracking.
Main Results:
- iKetSnFRs enabled rapid, sensitive detection of ketamine in mouse cortex.
- Ketamine was found to remain intracellularly and subcellularly engaged long after circulation clearance.
- Organelle-specific engagement of ketamine was visualized using targeted iKetSnFRs.
Conclusions:
- Ketamine exhibits persistent intracellular and subcellular engagement in neurons.
- These intracellular dynamics correlate with the prolonged antidepressant effects of ketamine.
- Provides a mechanistic basis for ketamine's rapid and enduring therapeutic actions.
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