Abstract
Purpose :
Interocular suppression is a quantifiable property and pathogenic driver of amblyopia. Despite the widely recognized importance, the underlying mechanisms serving interocular suppression are poorly understood. We aimed to deepen the understanding of interocular suppression and the effects of monocular deprivation in mouse visual cortex using 3 paradigms that employ visual evoked potentials (VEPs) with translational relevance.
Methods :
Juvenile (P32) mice underwent chronic electrode implantation. Awake VEPs were elicited by phase-reversing sinusoidal grating stimuli (0.05-0.4 cycles/degree) presented on a 3D monitor with polarized lenses at P35. We quantified interocular suppression through changes in VEP magnitude imparted by unilateral intravitreal tetrodotoxin injection (experiment 1), and dichoptic presentations of phase-offset gratings (experiment 2) or binocularly rivalrous grating orientations (experiment 3).
Results :
Retinal silencing via unilateral tetrodotoxin injection immediately augmented VEP magnitudes elicited through the uninjected eye by 1.5-2-fold on average, and the effect was spatial frequency-dependent. Prior 2-week monocular deprivation (P21-P35) increased the degree of VEP magnitude augmentation, consistent with greater tonic suppression in the context of amblyopia. Dichoptic, phase-offset gratings revealed a binocular balance point favoring the eye contralateral to the VEP recording hemisphere by a contrast ratio of ~2:1, reflective of the established contralateral bias of monocular VEP magnitudes. Preliminary data suggest that prior monocular deprivation shifted the binocular balance point in favor of the non-deprived eye. In the binocular rivalry paradigm, introduction of discordant (orthogonal) gratings reduced VEP magnitude in contrast- and spatial frequency-dependent manners. The effect on VEP magnitude was largely carried through reduction of the late, positive component of the VEP waveform. Prior monocular deprivation did not influence the effect of rivalry on VEP magnitude.
Conclusions :
We have validated 3 distinct measures of interocular suppression in mice. Monocular deprivation shifts 2 of these measures in favor of the non-deprived eye, reflective of human psychophysical results in amblyopia. We plan to leverage these measures to dissect the mechanism of interocular suppression to optimize the treatment of amblyopia.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.