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Review uncovers crosstalk-free actuator and indicator pairings in neural systems, highlighting strategies for simultaneous optical manipulation and readout.
Bidirectional optogenetics enables simultaneous optical readout and manipulation of neural activity. However, optical crosstalk between actuators and indicators impedes clean observation and control. This review surveys genetically encoded indicators and optogenetic actuators, and the mechanisms of crosstalk, then catalogues reported crosstalk-free pairings and trade-offs. Finally, we propose best-practice guidelines and identify future directions, including near-infra-red and two-photon modalities, protein engineering and computational correction.
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Travis et al. (2026) studied this question.
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