The ON Crossover Circuitry Shapes Spatiotemporal Profile in the Center and Surround of Mouse OFF Retinal Ganglion Cells

Abstract

Retinal ganglion cells (RGCs) are often grouped based on their functional properties. Many of these functional properties, such as receptive field (RF) size, are driven by specific retinal circuits. In this report, we determined the role of the ON bipolar cell (BC) mediated crossover circuitry in shaping the center and surround of OFF RGCs. We recorded from a large population of mouse RGCs using a multielectrode array (MEA) while pharmacologically removing the ON BC-mediated crossover circuit. OFF sustained and transient responses to whole field stimuli are lost under scotopic conditions, but maintained under photopic conditions. Though photopic light responses were grossly maintained, we found that photopic light response properties were altered. Using linear RF mapping, we found a significant reduction in the antagonistic surround and a decrease in size of the RF center. Using a novel approach to separate the distinct temporal filters present in the RF center, we see that the crossover pathway contributes specifically to the sluggish antagonistic filter in the center. These results provide new insight into the role of crossover pathways in driving RGCs and also demonstrate that the distinct inputs driving the RF center can be isolated and assayed by RGC activity.

Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs in mouse

“…5B (25). L-AP4 completely abolishes light responses in L-ON RGCs, but only reduces the light response and RF center size of L-OFF RGCs in control retinas (20). These L-AP4-induced changes are decreased with IOP elevation, suggesting some of the IOP-induced changes rely on cross-over circuits.…”

“…The rod ON BC to AII AC synapse (RBC-AIIAC) is an example upstream retinal synapse that is altered with IOP elevation (11). This synapse could contribute to center responses of OFF RGCs (13,20,25) and surround responses of ON RGCs (26). In addition, the RBC-AIIAC circuit would contribute to RF center size under scotopic conditions (15), which we also show is reduced in L-OFF RGCs.…”

“…The primary goal of this paper was to determine how RGC responses change with IOP elevation and which retinal circuits could (14,18,19) and center-surround structure (13,(20)(21)(22). We saw an IOP-induced decrease in firing rate in response to light offset for both OFF and ON-OFF RGCs.…”

“…Temporal properties of RGCs are also dependent on these upstream circuits (20,22), but the effect of IOP on temporal tuning has not been studied previously. We found that both ON and OFF RGCs accelerated their photopic temporal tuning.…”

“…However, we also found that scotopic temporal tuning is not altered with IOP elevation. One explanation for this is that under scotopic conditions the RBC-AIIAC circuit is the primary driver of RGC responses (14,19,20). Weakening this synapse would not lead to a relative increase in contribution of faster circuits, therefore RGC response kinetics would not change.…”