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Updated: Aug 6, 2026

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Optogenetic Manipulation of Neural Circuits During Monitoring Sleep/wakefulness States in Mice
Published on: June 19, 2019
A genetically encoded sensor of ionic stress links cellular proton dynamics to sleep
Zhijian Ji1, Bingying Wang1, Zhimin Ma1
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Science Advances
|July 24, 2026
Summary
Researchers developed a new sensor to visualize ionic stress in living organisms. This tool revealed that ionic rhythms during molting in C. elegans larvae regulate sleep behavior.
Area of Science:
- Cell Biology
- Neuroscience
- Biophysics
Background:
- Real-time monitoring of overall ionic strength in vivo is challenging.
- Existing biosensors target specific ions, not general ionic strength.
- Understanding ionic dynamics is crucial for cellular and organismal health.
Purpose of the Study:
- To develop a novel tool for visualizing ionic strength in living organisms.
- To investigate the role of ionic strength fluctuations during developmental stages.
- To explore the link between ionic changes and physiological processes like sleep.
Main Methods:
- Development of a genetically encoded nuclear translocation ionic sensor (GENTIS).
- Utilizing an automated microfluidic platform for longitudinal tracking of C. elegans.
- Inhibiting vacuolar-type adenosine triphosphatases (V-ATPases) to induce proton accumulation.
- Employing proton buffering with ammonium to assess the role of protons.
Main Results:
- GENTIS successfully visualized real-time ionic strength changes in vivo.
- C. elegans larvae exhibit synchronized, rhythmic ionic strength elevations during molting.
- Proton accumulation, via V-ATPases inhibition, triggers GENTIS translocation and behavioral quiescence (sleep).
- Disassembly of apical membrane V-ATPases during molting and stress correlates with proton accumulation and sleep.
Conclusions:
- GENTIS is a powerful tool for in vivo ionic strength dynamics.
- Proton ionic rhythms are integral to the regulation of developmental sleep.
- Ionic stress and its regulation play a significant role in organismal physiology.
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