This nonspecific cation channel opens when illuminated with blue light, depolarizing the cell [4, 6] to trigger action potentials cells with high temporal precision [5]. Since the initial discovery of ChR2, many modifications have been made to refine the kinetic properties.

For example, ChETA, engineered to address limitations of spike fidelity with ChR2, has faster temporal kinetics and can maintain reliable spike precision up to 200 Hz [7].

Halorhodopsins (NpHR), light-gated chloride pumps activated by yellow light, allow for temporally specific hyperpolarization with single spike precision [8–10].

Archaerhodopsin-3 (Arch), a yellow light-activated outward proton pump, is an increasingly popular tool for light-induced hyperpolarization to inhibit cellular activity. Arch recovers spontaneously from inactivation with a much shorter recovery time than NpHRs [11].

Arch currents continue to increase with increasing light intensity, while NpHRs saturate [11]. The increased light sensitivity of the ArchT variant, along with better membrane targeting, allows for improved neural silencing both at cell bodies and terminals [12].