Crosstalk-free optical indicator-actuator combinations for bidirectional optogenetics

Area of Science:

• Neuroscience
• Optogenetics
• Molecular Biology

Background:

• Bidirectional optogenetics offers simultaneous optical control and readout of neural activity.
• Optical crosstalk between actuators and indicators hinders precise neural circuit investigation.
• Genetically encoded tools are crucial for optogenetic applications.

Purpose of the Study:

• To review genetically encoded indicators and optogenetic actuators.
• To analyze the mechanisms and impact of optical crosstalk.
• To identify crosstalk-free tool pairings and propose solutions.

Main Methods:

• Literature review of optogenetic tools and crosstalk phenomena.
• Cataloguing of reported crosstalk-free indicator-actuator pairings.
• Analysis of trade-offs associated with tool selection.

Main Results:

• Identification of specific genetically encoded indicators and actuators.
• Detailed mechanisms of optical crosstalk are explained.
• A comprehensive list of crosstalk-free pairings is presented.

Conclusions:

• Addressing optical crosstalk is essential for advancing bidirectional optogenetics.
• Future directions include near-infrared and two-photon modalities, protein engineering, and computational correction.
• Best-practice guidelines are proposed to optimize tool selection and experimental design.