Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo.
basic_science · Level V
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- Record sourced from PubMed, PMID 38443508.
- Also identified by DOI 10.1038/s41592-024-02188-8 and PMC identifier 11377854.
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Abstract
The serotonergic system plays important roles in both physiological and pathological processes, and is a therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB<sub>5-HT</sub>) sensors and developed a red fluorescent GRAB<sub>5-HT</sub> sensor. These sensors exhibit excellent cell surface trafficking and high specificity, sensitivity and spatiotemporal resolution, making them suitable for monitoring 5-HT dynamics in vivo. Besides recording subcortical 5-HT release in freely moving mice, we observed both uniform and gradient 5-HT release in the mouse dorsal cortex with mesoscopic imaging. Finally, we performed dual-color imaging and observed seizure-induced waves of 5-HT release throughout the cortex following calcium and endocannabinoid waves. In summary, these 5-HT sensors can offer valuable insights regarding the serotonergic system in both health and disease.
Medical subject headings
- Serotonin
- Receptors, G-Protein-Coupled