Synaptic inputs to macaque intrinsically-photosensitive ganglion cells

Abstract

Purpose : The goal of this study was to identify the neurons that make synapses onto intrinsically-photosensitive retinal ganglion cells (ipRGCs) with somas located in the inner nuclear layer (INL), also known as the “displaced” type. The working hypothesis was that there were two distinct types of displaced ipRGCs, including one with input from OFF bipolar cells.

Methods : Three pieces of central macaque retina were fixed and stained en bloc with heavy metals. Sets of horizontal sections were acquired using scanning block-face serial electron microscopy. The ipRGCs were readily identified by the large diameters of their somas relative to others in the INL and by the lipofuscin granules they contained. They were analyzed using the Viking Annotation System and SBFSEM-tools. The presynaptic cells were also analyzed and identified morphologically.

Results : The volumes located about 2 mm temporal and 1.25 mm nasal to the center of the fovea each contained one ipRGC with its soma in the INL. Their dendrites had a large diameter and formed very sparse arbors confined entirely to the outermost stratum (S1) of the inner plexiform layer (IPL), and their axons were varicose. The volume located about 1.5 mm inferior to the center of the fovea contained somas of two ipRGCs, one similar to those in the other volumes and one smaller type with distal dendrites that gradually descended into the inner half of the IPL. All four ipRGCs received the majority of their inputs from amacrine cells. These likely included axons of dopaminergic amacrine cells with somas located outside the volumes. The smaller displaced ipRGC received virtually all of its excitatory input from five types of ON bipolar cells, mainly via the distal dendrites. The three larger displaced ipRGCs each received input from three types of OFF bipolar cells: DB1, DB2 and OFF midget (see figure). These would generate robust OFF responses in the larger displaced ipRGCs under a wide variety of conditions.

Conclusions : The larger type of displaced ipRGCs are likely the source of OFF responses recorded recently from human ipRGCs using microelectrode arrays. Input from the OFF pathway may account for the “paradoxical” pupillary responses seen in some patients with congenital stationary night blindness.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

A displaced ipRGC (yellow) received ribbon synapses (arrow) from 3 types of diffuse (DB) and midget (MB) OFF bipolar cells (green).