Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.

Synaptotagmin-9 (Syt9) is a Ca2+ sensor mediating fast synaptic release expressed in various parts of the brain. The presence and role of Syt9 in retina is unknown. We found evidence for Syt9 expression throughout the retina and created mice to conditionally eliminate Syt9 in a cre-dependent manner. We crossed Syt9fl/fl mice with Rho-iCre, HRGP-Cre, and CMV-Cre mice to generate mice in which Syt9 was eliminated from rods (rodSyt9CKO), cones (coneSyt9CKO), or whole animals (CMVSyt9). CMVSyt9 mice showed an increase in scotopic electroretinogram (ERG) b-waves evoked by bright flashes with no change in a-waves. Cone-driven photopic ERG b-waves were not significantly different in CMVSyt9 knockout mice and selective elimination of Syt9 from cones had no effect on ERGs. However, selective elimination from rods decreased scotopic and photopic b-waves as well as oscillatory potentials. These changes occurred only with bright flashes where cone responses contribute. Synaptic release was measured in individual rods by recording anion currents activated by glutamate binding to presynaptic glutamate transporters. Loss of Syt9 from rods had no effect on spontaneous or depolarization-evoked release. Our data show that Syt9 acts at multiple sites in the retina and suggest that it may play a role in regulating transmission of cone signals by rods.

Currently, electroretinograms (ERGs) are mainly recorded while using flashes as stimuli. In this review, we will argue that strong flashes are not ideal for studying visual information processing. ERG responses to periodic stimuli may be more strongly associated with the activity of post-receptoral neurons (belonging to different retino-geniculate pathways) and, therefore, be more relevant for visual perception. We will also argue that the use of periodic stimuli may be an attractive addition to clinically available retinal electrophysiological methods.

Symmetry is a salient visual feature in the natural world, yet the perception of symmetry may be influenced by how natural lighting conditions (e.g., shading) fall on the object relative to its symmetry axis. Here, we investigate how symmetry detection may interact with luminance polarity grouping, and whether this modulates neural responses to symmetry, as evidenced by the Sustained Posterior Negativity (SPN) component of Event-Related Potentials (ERPs). Stimuli were dot patterns arranged either symmetrically (reflection, rotation, translation) or quasi-randomly, and by luminance polarity about a grouping axis (i.e., black dots on one side and white dots on the other). We varied the relative angular separation between the symmetry and polarity-grouping axes: 0, 30, 60, 90 deg. Participants performed a two interval-forced-choice (2IFC) task indicating which interval contained the symmetrical pattern. We found that accuracy for the 0 deg polarity-grouped condition was higher compared to the single-polarity condition for rotation and translation (but not reflection symmetry), and higher than all other angular difference (30, 60, 90) conditions for all symmetry types. The SPN was found to be separated topographically into an early and late component, with the early SPN being sensitive to luminance polarity grouping at parietal-occipital electrodes, and the late SPN sensitive to symmetry over central electrodes. The increase in relative angular differences between luminance polarity and symmetry axes highlighted changes between cardinal (0, 90 deg) and other (30, 60 deg) angles. Critically, we found a polarity-grouping effect in the SPN time window for noise only patterns, which was related to symmetry type, suggesting a task/ symmetry pattern influence on SPN processes. We conclude that luminance polarity grouping can facilitate symmetry perception when symmetry is not readily salient, as evidenced by polarity sensitivity of early SPN, yet it can also inhibit neural and behavioral responses when luminance polarity and symmetry axes are not aligned.

Attention has been shown to modulate the visual evoked potential (VEP) recorded to reversing achromatic patterns. However, the chromatic onset VEP appears to be robust to attentional shifts. Functional magnetic resonance imaging (fMRI) responses to both chromatic and achromatic reversing patterns are also affected by attention. Resolution and comparison of these results is problematic due to differences in presentation mode, stimulus parameters, and the source of the response. Here, we report the results of experiments using comparable perceptual contrasts, pattern reversals, and a co-extensive and highly demanding multiple object tracking (MOT) task while exploring the effects of attentional modulation across both the chromatic (L − M) and (S − (L + M)) and the achromatic visual pathways. Our findings indicate that although achromatic VEPs are modulated by attention, chromatic VEPs are more robust to attentional modulation, even when using comparable stimulus presentation modes and in the presence of a highly demanding distractor task. In addition, we found that the majority of the modulation appears to be from a relative decrease in response due to the distractor task rather than a relative increase in response during heightened attention to the stimulus.

Recent reports suggest the ON and OFF pathways are differentially susceptible to selective vision loss in glaucoma. Thus, perimetric assessment of ON- and OFF-pathway function may serve as a useful diagnostic. However, this necessitates a developed understanding of normal ON/OFF pathway function around the visual field and as a function of input intensity. Here, using electroencephalography, we measured ON- and OFF-pathway biased contrast response functions in the upper and lower visual fields. Using the steady-state visually evoked potential paradigm, we flickered achromatic luminance probes according to a saw-tooth waveform, the fast phase of which biased responses towards the ON or OFF pathways. Neural responses from the upper and lower visual fields were simultaneously measured using frequency tagging - probes in the upper visual field modulated at 3.75 Hz, while those in the lower visual field modulated at 3 Hz. We find that responses to OFF/decrements are larger than ON/increments, especially in the lower visual field. In the lower visual field, both ON and OFF responses were well described by a sigmoidal non-linearity. In the upper visual field, the ON pathway function was very similar to that of the lower, but the OFF pathway function showed reduced saturation and more cross-subject variability. Overall, this demonstrates that the relationship between the ON and OFF pathways depends on the visual field location and contrast level, potentially reflective of natural scene statistics.