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Figure 1.
Adaptation of microbial opsins from nature for the optical control of neural activity
(A-C) Diagrams depicting the physiological responses of (A) archaerhodopsins and bacteriorhodopsins (light-driven outward proton pumps), (B) halorhodopsins (light-driven inward chloride pumps), and (C) channelrhodopsins (light-gated inward nonspecific cation channels), when expressed in the plasma membranes of neurons and exposed to light. (D) Demonstration of use of Halobacterium sodomense archaerhodopsin-3 (Arch) to mediate light-driven neural silencing in cortical pyramidal neurons of awake mice. Top: Neural activity in a representative neuron before, during, and after 5 seconds of yellow light illumination, shown as a spike raster plot (upper panel), and as a histogram of instantaneous firing rate averaged across trials (lower panel; bin size, 20 ms). Bottom: Population average of instantaneous firing rate before, during, and after yellow light illumination (black line, mean; gray lines, mean ± SE; n = 13 units). Adapted from [36]. (E) Demonstration of use of Natronomonas pharaonis halorhodopsin (Halo/NpHR) to mediate light-driven spike quieting, demonstrated for a representative hippocampal neuron in vitro. Top: (“Current injection”), neuronal firing of 20 spikes at 5 Hz, induced by pulsed somatic current injection (~300 pA, 4 ms). Middle: (“Light”), membrane hyperpolarization induced by two periods of yellow light, timed so as to be capable of blocking spikes 7–11 and spike 17 out of the train of 20 spikes. Bottom: (“Current injection + Light”), yellow light drives Halo to block neuron spiking (note absence of spikes 7–11 and of spike 17), while leaving intact the spikes elicited during periods of darkness. Adapted from [34]. (F) Demonstration of use of Chlamydomonas reinhardtii channelrhodopsin-2 (ChR2) to mediate light-driven spiking in two different hippocampal neurons, in response to the same train of blue light pulses (with timings selected from a Poisson distribution with mean interval λ = 100 ms). Adapted from [26]. BR, bacteriorhodopsin. |
