Fig. 1. Photoswitchable persistent responses in live-immunotagged macaque intrinsically photosensitive retinal ganglion cells (ipRGCs).

A. Antibody labeling in live tissue reveals diverse ipRGCs (inverted fluorescence images). Left, Z projection through a 13.5 μm thick volume containing the ganglion cell layer (GCL) and inner aspect of the inner plexiform layer (IPL). Arrowheads mark ipRGCs with somata in the GCL. Fluorescence in the upper left is from a blood vessel. Right, for the same XY position, a Z projection through a 29 μm thick volume containing the rest of the IPL and the inner aspect of the inner nuclear layer (INL). Arrowheads are in the same positions. B. Left to right, expanded views of two lightly-stained ipRGCs with somata in the GCL; an outer-stratifying ipRGC with its soma in the GCL (superficial and deep projections juxtaposed); and three outer-stratifying ipRGCs with somata displaced to the INL (corresponding to the orange box in “A”). C. Loose-patch recording. A pulse of short-wavelength light evokes persistent spiking near body temperature (35 °C). The inset shows spike waveforms on an expanded time base (excerpt position marked with an arrow) D. Top, Persistent spiking in another ipRGC. Peristimulus time histogram (PSTH) for three trials shown on right (23 °C). Bottom, For the same cell, chasing the short-wavelength light with long-wavelength light curtails the persistent response (PSTH from three trials). E. Perforated-patch recording in voltage clamp (−80 mV, 23 °C). Short- and long-wavelength switching of persistent photocurrent. Long-wavelength light evokes current because some photon absorptions cycle melanopsin molecules through the signaling state, even if the photoequilibrium favors low occupancy of this state. Response traces are low-pass filtered at 2 Hz. F. 2 s long segments of the same recording, keyed to time points in “D.” Traces are low-pass filtered at 20 Hz. Synaptic antagonists. (For all figures, see Methods for stimulus details.)