Conserved circuits for direction selectivity in the primate retina

Abstract

The detection of motion direction is a fundamental visual function and a classic model for neural computation. In the non-primate retina, direction selectivity arises in starburst amacrine cell (SAC) dendrites, which provide selective inhibition to direction-selective retinal ganglion cells (dsRGCs). Although SACs are present in primates, their connectivity and the existence of dsRGCs remain open questions. Here, we present a connectomic reconstruction of the primate ON SAC circuit from a serial electron microscopy volume of the macaque central retina. We show that the structural basis for the SACs' ability to confer directional selectivity on postsynaptic neurons is conserved. SACs selectively target a candidate homolog to the mammalian ON-sustained dsRGCs that project to the accessory optic system (AOS) and contribute to gaze-stabilizing reflexes. These results indicate that the capacity to compute motion direction is present in the retina, which is earlier in the primate visual system than classically thought.

Keywords: accessory optic system; bipolar cells; connectomics; direction selectivity; motion processing; primate; retina; retinal circuitry; retinal ganglion cells; starburst amacrine cells.

Figure 1.. ON SACs of the primate retina.

(A) 3D reconstructions of representative ON SACs and isolated ON SAC dendrites. (B) Side view of 8 ON SAC reconstructions. (C) ON SAC stratification depth in the inner plexiform layer (IPL), 67.6 ± 11.0% (mean ± SD, n = 8 SACs). Scale bars are 20 μm.

Figure 2.. ON SAC synaptic architecture.

(A-B) Locations of ribbon synaptic input, conventional synaptic input and output synapses along two ON SAC’s dendritic fields. Scale bars are 20 μm. (C) The distance from the soma for each synapse type from the 2 ON SACs. See also Figure S1.

Figure 3.. Bipolar cell input to ON SACs

(A) Locations of ribbon synaptic input to an ON SAC, colored by bipolar cell type (n = 33 DB4, 5 DB5 and 19 ON midget bipolar cell synapses). (B) Radial distance from the SAC soma for each bipolar cell type. (C) Comparison of distance from the SAC soma and stratification within the IPL for bipolar cell synapses. (D-F) Reconstructions of presynaptic axon terminals of ON midget, DB4 diffuse and DB5 diffuse bipolar cells, respectively. Scale bars are 20 μm.

Figure 4.. ON SAC synaptic output to RGCs.

(A) Frequency of SAC output synapses to RGCs (46), SACs (16), non-SAC amacrine cells (8) and bipolar cells (1). (B) 3D reconstruction of representative “wrap-around” synapses between the ON SAC and RGC in 4E. EM micrographs show five distinct synapses between the two cells. (C) 3D reconstruction of the RGC in 4A-B. (D) Co-stratification profile of the rmRGC with the ON SACs from 1C. (E) Light blue markers show locations of synapses between the ON SAC and RGC. Note the co-fasciculation between the two cells. (F) Side view of the RGC in 4C with ON SACs in gray. Scale bars in 4B are 1 μm, the rest are 20 μm. See also Figure S2–S4.

Figure 5.. Connectivity of SACs and rmRGCs.

(A) Locations of SAC synaptic input, colored by dendritic angle. (B) Polar histogram of the dendritic angles for the synapses in 5A. (C) Population of 3 rmRGCs. (D) Co-fasciculation of rmRGC dendrites. (E) As in Figure 4B, but with the second rmRGC from Fig. 5D added in green. Note the close proximity to the first rmRGC and SAC, but lack of input from the SAC. (F) As in Figure 4E, but with an arrow pointing to the SAC’s two synapses onto the second rmRGC marked in green. Scale bars in 5E are 1 μm, the rest are 20 μm.

Figure 6.. Retrograde labeling of RGCs projecting to the NOT-DTN.

(A) Direction-selective response properties recorded from the NOT-DTN to horizontal smooth pursuit. The monkey’s horizontal eye movements (red) follow the horizontal position of the target (blue). Scale bar is 1 second. (B) RGC soma identified by fluorescent rhodamine dextran granules (633 nm excitation). (C) Cell fill of rhodamine-labeled RGC, electrode to the bottom right (488 nm excitation). (D) Tracing of the dendritic field in 6C, omitting the axon. Scale bars are 20 μm. See also Figure S5 and S6.

Figure 7.. Comparison of rmRGC dendritic field with other common primate RGCs.

An rmRGC (black) compared to the three most common and well-studied primate RGCs: parasol (red), midget (green) and small bistratified (blue). Scale bar is 20 μm. See also Figure S7.