Abstract
Purpose :
An asymmetry exists between the fidelity of the optokinetic reflex (OKR) in the dorsal-to-ventral (“Inferior”) and ventral-to-dorsal (“Superior”) directions. The neural underpinnings of this asymmetry are unknown. We made electrophysiological recordings from mouse ON direction-selective retinal ganglion cells (oDSGCs) to test the hypothesis that behavioral asymmetries in vertical OKR are associated with physiological asymmetries between oDSGCs that prefer Inferior and Superior motion.
Methods :
A retrograde tracer was injected into the projection nucleus of Inferior and Superior oDSGCs in adult, wild-type mice of both sexes (N=33). Following dark-adaptation, retinas were harvested for electrophysiology. We compared the direction tuning of Inferior and Superior oDSGCs by making patch-clamp recordings from labeled cells in response to a drifting bar. Direction selectivity indices (DSIs) and tuning curve widths were compared across cell types and recording conditions (mean±SEM, rank sum). A computational model was built to examine the relationship between input currents and spike tuning curves. Vertical OKR was measured in a separate cohort of head-fixed mice.
Results :
Our data indicate that Inferior oDSGCs spike less (spikes per stimulus: Inf. 27.40±1.57, Sup. 38.71±2.04, p<0.0001), are more direction-selective (DSI: Inf. 0.37±0.01, Sup. 0.28±0.01, p<0.001), and have narrower tuning curves (width at half maximum (degrees): Inf. 213.89±6.36, Sup. 258.49±6.12, p<0.0001) than Superior oDSGCs (n = 155 Inf., 115 Sup.). Voltage-clamp recordings demonstrated that this asymmetry is not explained by the canonical model of retinal direction selectivity, as there was no difference in inhibitory inputs across cell types (p>0.05 for peak IPSC of each stimulus direction). Instead, we found a difference in the magnitude of directionally untuned excitation across oDSGC types (p<0.02 for peak EPSC of each stimulus direction). Current-clamp experiments and modeling revealed a mechanism by which such excitation influences tuning curve shape. Finally, we found an analogous asymmetry in the vertical OKR of behaving mice.
Conclusions :
Our results demonstrate that Inferior and Superior oDSGCs encode motion asymmetrically due to disproportionate excitatory input, and link this phenomenon to corresponding behavioral asymmetries in vertical OKR.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.