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Automated Functional Screening for Modulators of Optogenetically Activated Neural Responses in Living Organisms
Ross C Lagoy1, Eric Larsen1, Dirk R Albrecht2,3
1Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
Methods in Molecular Biology (Clifton, N.J.)
|September 1, 2020
Summary
This study presents an automated, all-optical method for screening chemical compounds by measuring optogenetically induced neural responses in vivo. The high-throughput assay enables long-term assessment of neural activity and drug effects over 12 hours.
Area of Science:
- Neuroscience
- Pharmacology
- Biotechnology
Background:
- All-optical methods offer advantages for in vivo brain function analysis.
- Optogenetics enables simultaneous neural activation and optical readout of activity.
- High-throughput screening of neural function in vivo is crucial for drug discovery.
Purpose of the Study:
- To develop an automated method for recording optogenetically activated neural responses in hydrogel-embedded organisms.
- To enable high-throughput screening of chemical compounds for their effects on neural activity.
- To assess the time course of bioactivity over extended periods (12+ hours).
Main Methods:
- Utilized automated microscopy and multiwell plate format for long-term recording.
- Employed optogenetic stimulation for targeted neural activation.
- Measured neural responses using fluorescent calcium reporters in vivo.
- Applied hydrogel embedding for maintaining organism viability and stability.
Main Results:
- Successfully recorded optogenetically activated neural responses over many hours.
- Demonstrated suppression of neural responses with voltage-gated calcium channel blockers.
- Conducted a full-plate screen of 320 chemicals, including controls, in a single experiment.
Conclusions:
- The developed method is suitable for high-throughput screening of chemical compounds affecting neural function.
- This approach allows for the assessment of dynamic neural responses and bioactivity over extended durations.
- Automated, all-optical in vivo screening accelerates the discovery of neuroactive compounds.
