Embryonic hyperglycemia perturbs the development of specific retinal cell types, including photoreceptors

Diabetes is linked to various long-term complications in adults, such as neuropathy, nephropathy, and diabetic retinopathy. Diabetes poses additional risks for pregnant women, because glucose passes across the placenta, and excess maternal glucose can result in diabetic embryopathy. While many studies have examined the teratogenic effects of maternal diabetes on fetal heart development, little is known about the consequences of maternal hyperglycemia on the development of the embryonic retina. To address this question, we investigated retinal development in two models of embryonic hyperglycemia in zebrafish. Strikingly, we found that hyperglycemic larvae displayed a significant reduction in photoreceptors and horizontal cells, whereas other retinal neurons were not affected. We also observed reactive gliosis and abnormal optokinetic responses in hyperglycemic larvae. Further analysis revealed delayed retinal cell differentiation in hyperglycemic embryos that coincided with increased reactive oxygen species (ROS). Our results suggest that embryonic hyperglycemia causes abnormal retinal development via altered timing of cell differentiation and ROS production, which is accompanied by visual defects. Further studies using zebrafish models of hyperglycemia will allow us to understand the molecular mechanisms underlying these effects.

Response Properties of Optic Flow Neurons in the Accessory Optic System of Hummingbirds vs. Zebra Finches and Pigeons

Optokinetic responses function to maintain retinal image stabilization by minimizing optic flow that occurs during self-motion. The hovering ability of hummingbirds is an extreme example of this behaviour. Optokinetic responses are mediated by direction-selective neurons with large receptive fields in the accessory optic system (AOS) and pretectum. Recent studies in hummingbirds showed that, compared to other bird species, (i) the pretectal nucleus lentiformis mesencephali (LM) is hypertrophied, (ii) LM has a unique distribution of direction preferences, and (iii) LM neurons are more tightly tuned to stimulus velocity. In this study, we sought to determine if there are concomitant changes in the nucleus of the basal optic root (nBOR) of the AOS. We recorded the visual response properties of nBOR neurons to largefield drifting random dot patterns and sine wave gratings in Anna's hummingbirds and zebra finches and compared these with archival data from pigeons. We found no differences with respect to the distribution of direction preferences: Neurons responsive to upwards, downwards and nasal-to-temporal motion were equally represented in all three species, and neurons responsive to temporal-to-nasal motion were rare or absent (<5%). Compared to zebra finches and pigeons, however, hummingbird nBOR neurons were more tightly tuned to stimulus velocity of random dot stimuli. Moreover, in response to drifting gratings, hummingbird nBOR neurons are more tightly tuned in the spatio-temporal domain. These results, in combination with specialization in LM, supports a hypothesis that hummingbirds have evolved to be "optic flow specialist" to cope with the optomotor demands of sustained hovering flight.

A retinal circuit that vetoes optokinetic responses to fast visual motion

Optokinetic nystagmus (OKN) is a visuomotor reflex that works in tandem with the vestibulo-ocular reflex (VOR) to stabilize the retinal image during self-motion. OKN requires information about both the direction and speed of retinal image motion. Both components are computed within the retina because they are already encoded in the spike trains of the specific class of retinal output neurons that drives OKN ─ the ON direction-selective ganglion cells (ON DSGCs). The synaptic circuits that shape the directional tuning of ON DSGCs, anchored by starburst amacrine cells, are largely established. By contrast, little is known about the cells and circuits that account for the slow speed preference of ON DSGCs and, thus, of OKN that they drive. A recent study in rabbit retina implicates feedforward glycinergic inhibition as the key suppressor of ON DSGC responses to fast motion. Here, we used serial-section electron microscopy, patch recording, pharmacology, and optogenetic and chemogenetic manipulations to probe this circuit in mouse retina. We confirm a central role for feedforward glycinergic inhibition onto ON DSGCs and identify a surprising primary source for this inhibition ─ the VGluT3 amacrine cell (VG3 cell). VG3 cells are retinal interneurons that release both glycine and glutamate, exciting some neurons and inhibiting others. Their role in suppressing the response of ON DSGCs to rapid global motion is surprising. VG3 cells had been thought to provide glutamatergic excitation to ON-DSGCs, not glycinergic inhibition, and because they have strong receptive fields surrounds which might have been expected to render them unresponsive to global motion. In fact, VG3 cells are robustly activated by the sorts of fast global motion that suppress ON DSGCs and weaken optokinetic responses as revealed by dendritic Ca+2 imaging, since surround suppression is less prominent when probed with moving gratings than with spots. VG3 cells excite many ganglion cell types through their release of glutatmate. We confirmed that for one such type, the ON-OFF DSGCs, VG3 cells enhance the response to fast motion in these cells, just as they suppress it in ON DSGCs. Together, our results assign a novel function to VGluT3 cells in shaping the velocity range over which retinal slip drives compensatory image stabilizing eye movements. In addition, fast speed motion signal from VGluT3 cells is used by ON-OFF DSGCs to extend the speed range over which they respond, and might be used to shape the speed tuning or temporal bandwidth of the responses of other RGCs.

Echolocating toothed whales use ultra-fast echo-kinetic responses to track evasive prey

Visual predators rely on fast-acting optokinetic responses to track and capture agile prey. Most toothed whales, however, rely on echolocation for hunting and have converged on biosonar clicking rates reaching 500/s during prey pursuits. If echoes are processed on a click-by-click basis, as assumed, neural responses 100× faster than those in vision are required to keep pace with this information flow. Using high-resolution biologging of wild predator-prey interactions, we show that toothed whales adjust clicking rates to track prey movement within 50–200 ms of prey escape responses. Hypothesising that these stereotyped biosonar adjustments are elicited by sudden prey accelerations, we measured echo-kinetic responses from trained harbour porpoises to a moving target and found similar latencies. High biosonar sampling rates are, therefore, not supported by extreme speeds of neural processing and muscular responses. Instead, the neurokinetic response times in echolocation are similar to those of tracking responses in vision, suggesting a common neural underpinning.

Influence of Aging on the Retina and Visual Motion Processing for Optokinetic Responses in Mice

The decline in visual function due to normal aging impacts various aspects of our daily lives. Previous reports suggest that the aging retina exhibits mislocalization of photoreceptor terminals and reduced amplitudes of scotopic and photopic electroretinogram (ERG) responses in mice. These abnormalities are thought to contribute to age-related visual impairment; however, the extent to which visual function is impaired by aging at the organismal level is unclear. In the present study, we focus on the age-related changes of the optokinetic responses (OKRs) in visual processing. Moreover, we investigated the initial and late phases of the OKRs in young adult (2–3 months old) and aging mice (21–24 months old). The initial phase was evaluated by measuring the open-loop eye velocity of OKRs using sinusoidal grating patterns of various spatial frequencies (SFs) and moving at various temporal frequencies (TFs) for 0.5 s. The aging mice exhibited initial OKRs with a spatiotemporal frequency tuning that was slightly different from those in young adult mice. The late-phase OKRs were investigated by measuring the slow-phase velocity of the optokinetic nystagmus evoked by sinusoidal gratings of various spatiotemporal frequencies moving for 30 s. We found that optimal SF and TF in the normal aging mice are both reduced compared with those in young adult mice. In addition, we measured the OKRs of 4.1G-null (4.1G–/–) mice, in which mislocalization of photoreceptor terminals is observed even at the young adult stage. We found that the late phase OKR was significantly impaired in 4.1G–/– mice, which exhibit significantly reduced SF and TF compared with control mice. These OKR abnormalities observed in 4.1G–/– mice resemble the abnormalities found in normal aging mice. This finding suggests that these mice can be useful mouse models for studying the aging of the retinal tissue and declining visual function. Taken together, the current study demonstrates that normal aging deteriorates to visual motion processing for both the initial and late phases of OKRs. Moreover, it implies that the abnormalities of the visual function in the normal aging mice are at least partly due to mislocalization of photoreceptor synapses.