Glena Travis, Hallur Reynisson, Anai Gonzalez-Cordero, Stefano Palomba
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.