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.

In the frog Xenopus laevis, the isthmotectal projection, which relays input from the ipsilateral eye, exhibits anatomical reorganization following surgical eye rotation performed during tadpole stages while the isthmotectal projection in the frog Rana pipiens fails to show reorganization. This plasticity has been shown to be dependent upon activation of the N-methyl-D-aspartate (NMDA) receptor located on tectal cell dendrites. The reorganization process in Xenopus is hypothesized to employ a Hebbian mechanism requiring correlated firing of ipsilateral and contralateral inputs to a given tectal cell; when an ipsilateral axon synapses onto a tectal cell that receives input from a contralateral axon with a matching receptive-field location, the correlation in activity triggers stabilization of the ipsilateral synapse. However, in neither Xenopus nor Rana do ipsilateral and contralateral inputs begin to fire simultaneously in response to a given visual stimulus; the ipsilateral input is delayed because it reaches the tectum indirectly, through a polysynaptic relay via the opposite tectum and nucleus isthmi. The objective of this experiment was to test whether there is a significant difference in this intertectal delay between Xenopus laevis and Rana pipiens in order to determine whether intertectal delay could be a contributing factor in this species-specific ability to exhibit visual plasticity. We have found that intertectal delay is 26.16 ms longer in Rana pipiens (36.53 ms) than in Xenopus laevis (10.37 ms).

Normal, regenerating, and developing optic nerves of the goldfish were studied utilizing a monoclonal antibody (mAb) 1E1T which has specificity for Müller cells in the retina, radial ghal cells in the tectum, and non-neuronal cells in the optic nerve.

Sections of the normal optic nerve revealed longitudinally oriented chains of non-neuronal cells, that were 4–8 cells long The number of chains in the normal nerve was very few. In addition, short acellular septa, probably the connective tissue septa, were also labeled with mAb 1E1T. Sections of crushed optic nerves showed an increase in the antigen recognized by mAb 1E1T within the septa and new septa were now visualized. Furthermore, the existing septa were longer and extended the length of the optic nerve. The formation and elongation of the septa occurred as early as 3 day postcrush. Between 3 and 11 d postcrush, there was heavy labeling of the septa and a large accumulation of non-neuronal cells at the crush site. At 3 months postcrush, the accumulation of non-neuronal cells labeled by mAb 1E1T were no longer visible but heavy labeling of the septa was still apparent.

Your journal enters its third decade with the publication of this issue. The first volume, published in 1988, appeared in quarterly issues, but moved to bi-monthly production in 1989, and then monthly release from 1990 through 1992. Two volumes appeared each year during 1989–1992, accounting for the fact that this twenty-first year coincides with volume 25. In 1993, it returned to bi-monthly publication, remaining so for the past 15 years. During this period, other vision-related journals have made their debut, but Visual Neuroscience remains a premier venue for publishing fundamental research in the neurobiology of vision.

The purpose of this brief communication is to make publicly available three unpublished manuscripts on the organization of retinal ganglion cells in the tree shrew. The manuscripts were authored in 1986 by Dr. Edward DeBruyn, a PhD student in the laboratory of the late Dr. Vivien Casagrande at Vanderbilt University. As diurnal animals closely related to primates, tree shrews are ideally suited for comparative analyses of visual structures including the retina. We hope that providing this basic information in a citable form inspires other groups to pursue further characterization of the tree shrew retina using modern techniques.

Chromatic assimilation is a shift toward the color of nearby light. Several studies conclude that a neural process contributes to assimilation but the neural locus remains in question. Some studies posit a peripheral process, such as retinal receptive-field organization, while others claim the neural mechanism follows depth perception, figure/ground segregation, or perceptual grouping. The experiments here tested whether assimilation depends on a neural process that follows stereoscopic depth perception. By introducing binocular disparity, the test field judged in color was made to appear in a different depth plane than the light that induced assimilation. The chromaticity and spatial frequency of the inducing light, and the chromaticity of the test light, were varied. Chromatic assimilation was found with all inducing-light sizes and chromaticities, but the magnitude of assimilation did not depend on the perceived relative depth planes of the test and inducing fields. We found no evidence to support the view that chromatic assimilation depends on a neural process that follows binocular combination of the two eyes' signals.

Activation of Group III metabotropic glutamate receptors (mGluRs) by L(+)-2-amino-4-phosphonobutyric acid (L-AP4) has different effects on in vitro slice preparations of visual cortex (Jin & Daw, 1998) as compared with in vivo recordings from somatosensory cortex (Wan & Cahusac, 1995). To investigate the role of Group III mGluRs in the cat visual cortex, in vivo recordings were made of neurons in area 17 of the visual cortex of kittens and adult cats at different ages and the effect of iontophoretic application of L-AP4 (100 mM) was examined. Application of L-AP4 resulted in an increase of the spontaneous activity and visual response of neurons to visual stimulation, the former more than the latter. The effect of L-AP4 was greatest at 3–5 weeks of age with the effect on the visual response declining more rapidly than the effect on spontaneous activity. Consistent with work in rat cortex (Jin & Daw, 1998), the effect of L-AP4 was significantly greater in upper and lower layers than in middle layers. Whole-cell in vitro recordings from slices of rat visual cortex indicated that L-AP4 (50 mM) did not increase the number of spikes elicited by increasing levels of current injections. These results confirm that L-AP4 increases activity in vivo and reasons for the discrepancy with the in vitro results are discussed.

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.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only anterogradely to drive behavioral responses, but also retrogradely to some amacrine interneurons to modulate retinal physiology. We previously found that all displaced amacrine cells with spiking, tonic excitatory photoresponses receive gap-junction input from ipRGCs, but the connectivity patterns and functional roles of ipRGC-amacrine coupling remained largely unknown. Here, we injected PoPro1 fluorescent tracer into all six types of mouse ipRGCs to identify coupled amacrine cells, and analyzed the latter’s morphological and electrophysiological properties. We also examined how genetically disrupting ipRGC-amacrine coupling affected ipRGC photoresponses. Results showed that ipRGCs couple with not just ON- and ON/OFF-stratified amacrine cells in the ganglion-cell layer as previously reported, but also OFF-stratified amacrine cells in both ganglion-cell and inner nuclear layers. M1- and M3-type ipRGCs couple mainly with ON/OFF-stratified amacrine cells, whereas the other ipRGC types couple almost exclusively with ON-stratified ones. ipRGCs transmit melanopsin-based light responses to at least 93% of the coupled amacrine cells. Some of the ON-stratifying ipRGC-coupled amacrine cells exhibit transient hyperpolarizing light responses. We detected bidirectional electrical transmission between an ipRGC and a coupled amacrine cell, although transmission was asymmetric for this particular cell pair, favoring the ipRGC-to-amacrine direction. We also observed electrical transmission between two amacrine cells coupled to the same ipRGC. In both scenarios of coupling, the coupled cells often spiked synchronously. While ipRGC-amacrine coupling somewhat reduces the peak firing rates of ipRGCs’ intrinsic melanopsin-based photoresponses, it renders these responses more sustained and longer-lasting. In summary, ipRGCs’ gap junctional network involves more amacrine cell types and plays more roles than previously appreciated.

At certain temporal frequencies, the human cone flicker electroretinogram (ERG) contains multiple additional responses following the termination of a flicker train. The purpose of this study was to determine whether these poststimulus responses are a continuing response to the terminated flicker train or represent the oscillation of a resonant system. ERGs were recorded from 10 visually normal adults in response to full-field sinusoidally modulated flicker trains presented against a short-wavelength rod-saturating adapting field. The amplitude and timing properties of the poststimulus responses were evaluated within the context of a model of a second-order resonant system. At stimulus frequencies between 41.7 and 71.4 Hz, the majority of subjects showed at least three additional ERG responses following the termination of the flicker train. The interval between the poststimulus responses was approximately constant across stimulus frequency, with a mean of 14.4 ms, corresponding to a frequency of 69.4 Hz. The amplitude and timing characteristics of the poststimulus ERG responses were well described by an underdamped second-order system with a resonance frequency of 70.3 Hz. The observed poststimulus ERG responses may represent resonant oscillations of retinal ON bipolar cells, as has been proposed for electrophysiological recordings of poststimulus responses from retinal ganglion cells. However, further investigation is required to determine the types of retinal neurons involved in the generation of the poststimulus responses of the human flicker ERG.

Two synapse-rich layers are well recognized in the mammalian retina, the inner and outer plexiform layers. However, synapses occur also in other layers, particularly in the innermost nerve fiber layer. These synapses form a tenuous layer at times referred to as the superficial plexiform layer. We have found that staining for GABAA receptors in whole-mounted rabbit retina demonstrates this layer. It is most well developed in the region of the visual streak 2–4 mm below the center of the myelinated streak and is very sparse in other parts. Most or all of the processes in the plexus originate from cells in the ganglion cell layer.

The common brush-tailed possum Trichosurus vulpecula is a small diprotodont marsupial common to both urban and natural environments. This is the first analysis of the neurotransmitter content of its retinal cells and, as the possum is a nocturnal forager, it was appropriate to begin with the dopaminergic amacrine cells that form an essential link in the modulation of the rod pathways subserving nocturnal vision. These results were compared with those from another diprotodont, the marsupial wallaby or quokka (Dann, 1996) to establish whether the dopaminergic systems were similar between these two diprotodont marsupials and also to compare these findings with those of other mammals. This study describes a population of amacrine cells in the possum retina that were immunolabelled with an antibody raised against tyrosine hydroxylase (TH). These TH-immunoreactive (IR) cells were located within the inner nuclear layer (INL) and their dendrites predominantly ramified within the most sclerad layers of the inner plexiform layer (IPL). The TH-IR amacrines formed a sparse cell population, of around 2400 cells, distributed over the entire retina. There was little evidence of a concentration gradient except for a slight elevation in density in the naso-temporal axis in dorsal retina. The formation of rings within the dendritic plexus, a feature common to TH-IR cells in other species, was also present in the possum and these appeared relatively frequently. This latter finding was rather unexpected since, in the marsupial quokka (Dann, 1996), the TH-IR dendrites formed fewer rings despite having the same density of TH-IR amacrines as the possum. This suggests that there may be subtle differences in the way the rod pathways are interconnected even within the same marsupial group and may also be a reflection of relative rod dominance across species.

Direction-selective responses were recorded from neurons in the dorsal terminal nucleus (DTN) of the cat accessory optic system before and after intravitreal injections of tetrodotoxin (TTX) into the contralateral eye. After approximately 100 min, direction-selective responses driven through stimulation of the contralateral, injected eye were reduced on average by 90%, while direction-selective responses driven through stimulation of the ipsilateral, uninjected eye were not significantly reduced. By 200 min postinjection, ipsilateral direction-selective responses were either equal to or sometimes greater than control values. In the final stages of these experiments (i.e. between 390–830 min after contralateral eye injections), ipsilateral eye responses were on average 30% higher than control. The effects of retinal blockade of the contralateral eye by TTX show that input from the ipsilateral eye alone is sufficient to mediate direction-selective responses in DTN cells. These results and those observed following bicuculline eye injections reported previously (Grasse et al. 1990) demonstrate that direction-selective responses in the DTN driven through stimulation of the contralateral and ipsilateral eyes arise from independent neural mechanisms located in the retina and visual cortex, respectively. Moreover, these findings also suggest that the contralateral eye exerts an inhibitory influence over ipsilateral eye responses which is diminished by TTX injections into the contralateral eye.

The cingulate cortex (CG) and the adjacent region designated as the splenial visual area (SVA) project to areas of the extrageniculate thalamic system that are concerned with processing visual information. En route to the thalamus, they pass through the thalamic reticular nucleus (TRN), an important source of thalamic inhibition. We wished to determine whether SVA axon collaterals projected to the previously defined visual sector of the TRN or a separate projection zone and did this differ from the projection zone of CG. We iontophoretically injected different neuroanatomical tracers into several locations within CG/SVA and traced the labeled axons through the TRN. The CG and SVA have a projection zone that only partially overlaps the dorsorostral regions of the visuocortical projection zone; there was no evidence to suggest separate SVA and CG zones or tiers of label within the TRN. The projection formed only a weak topographic map in the TRN, which is largely defined in the rostrocaudal axis and is similar to that of the area 7 projection; both projections have a high degree of overlap in the dorsal TRN. We postulate that CG/SVA may be involved in the initiation of orientation behaviors via stimulation of thalamic nuclei and attentional mechanisms of the TRN.

The nucleus isthmi (NI) of the frog receives input from the ipsilateral optic tectum and projects back to both optic tecta. After ablation of NI, frogs display no visually elicited prey-catching or threat avoidance behavior. Neural mechanisms that underlie the loss of such important behavior have not been solved. Electrophysiological examination of the contralateral isthmotectal projection has proved that it contributes to binocular vision. On the other hand, there are very few physiological investigations of the ipsilateral isthmotectal projection. In this study, current source density (CSD) analysis was applied to contra- and ipsilateral isthmotectal projections. The contralateral projection produced monosynaptic sinks in superficial layers and in layer 8. The results confirmed former findings obtained by single unit recordings. The ipsilateral projection elicited a prominent monosynaptic sink in layer 8. Recipient neurons were located in layers 6–7. These results, combined with those from the former intracellular study, led to the following neuronal circuit. Afferents from the ipsilateral NI inhibit non-efferent pear shaped neurons in the superficial layers, and strongly excite large ganglionic neurons projecting to the descending motor regions. Thus feedback to the output neurons strengthens the visually elicited responses.