Our previous studies suggested that reduced choroidal blood flow (CBF) occurs with manipulations that yield myopic eye growth and that these reductions are primarily a consequence of the ocular enlargement. We could not entirely rule out the possibility, however, that reductions in CBF are at least to some extent antecedent and causal to the ocular enlargement. We therefore in the present study examined the effects on eye size of artificially reducing CBF by unilaterally transecting the choroidal nerves of the ciliary ganglion in four-day-old chicks. For comparison, we also transected the ciliary nerves in a second group of chicks or transected both ciliary and choroidal nerves in a third group of chicks. The effects of the nerve transections were evaluated in comparison to the effects of the orbital surgery itself (without nerve transection) in a fourth group termed the sham-operated control group. Two weeks after transection, CBF was measured using laser Doppler velocimetry, the ocular axial, nasotemporal and dorsoventral lengths were measured, and the eyes weighed.

The results showed that CBF in birds with either choroidal nerve cuts or choroidal plus ciliary nerve cuts was greatly reduced in the treated eye (20–40% of nontreated eye). The treated eyes of these birds also showed gross depigmentation and histologically evident loss of the outer retina, most typically in the temporal retina. Birds with ciliary nerve cuts showed increased CBF in both eyes (131% right eye and 154% left eye compared to shams). Since ciliary nerve cuts yield fixed dilated pupils, increased CBF with ciliary nerve cuts appears consistent with the previously reported involvement of the choroidal nerves within a neural circuit subserving light-mediated upregulation of CBF. Clear effects on eye size were observed in the treated eyes in each group. The sham surgery alone yielded slight enlargement of the right eye compared to left eye, particularly in the axial dimension. In the choroidal nerve and the both nerve cut groups, nasotemporal and dorsoventral elongation were slightly diminished in the treated eyes compared to the sham-treated eyes. In contrast, enlargement of the right eye was slightly enhanced in the ciliary nerve cut group compared to the sham-treated eyes. The overall results suggest that large decreases in CBF do not enhance myopic eye growth, although large increases in CBF may.

Lateral suprasylvian visual cortex in the cat has been studied extensively, but its retinotopic organization remains controversial. Although some investigators have divided this region into many distinct areas, others have argued for a simpler organization. A clear understanding of the region’s retinotopic organization is important in order to define distinct areas that are likely to subserve unique visual functions. We therefore reexamined the map of the lower visual field in the striate-recipient region of lateral suprasylvian cortex, a region we refer to as the lateral suprasylvian area, LS.

A dual mapping approach was used. First, receptive fields were plotted at numerous locations along closely spaced electrode penetrations; second, different anterograde tracers were injected at retinotopically identified sites in area 17, yielding patches of label in LS. To visualize the resulting data, suprasylvian cortex was flattened with the aid of a computer.

Global features of the map reported in many earlier studies were confirmed. Central visual field was represented posteriorly, and elevations generally shifted downward as one moved anteriorly. Often (though not always) there was a progression from peripheral locations towards the vertical meridian as the electrode moved down the medial suprasylvian bank.

The map had some remarkable characteristics not previously reported in any map in the cat. The vertical meridian’s representation was split into two pieces, separated by a gap, and both pieces were partially internalized within the map. Horizontal meridian occupied the gap. The area centralis usually had a dual representation along the posterior boundary of the lower field representation, and other fragments of visual field were duplicated as well. Finally, magnification appeared to change abruptly and unexpectedly, so that compressed regions of representation adjoined expanded regions. Despite its complexity, we found the map to be more orderly than previously thought. There was no clearcut retinotopic basis on which to subdivide LS’s lower field representation into distinct areas.

Bipolar cells are not only important for visual processing but input from these cells may underlie the reorganization of ganglion cell dendrites in the inner plexiform layer (IPL) during development. Because little is known about the development of bipolar cells, here we have used immunocytochemical markers and dye labeling to identify and follow their differentiation in the neonatal ferret retina. Putative cone bipolar cells were immunoreacted for calbindin and recoverin, and rod bipolar cells were immunostained for protein kinase C (PKC). Our results show that calbindin-immunoreactive cone bipolar cells appear at postnatal day 15 (P15), at which time their axonal terminals are already localized to the inner half of the IPL. By contrast, recoverin-immunoreactive cells with terminals in the IPL are present at birth, but many of these cells may be immature photoreceptors. By the second postnatal week, recoverin-positive cells resembling cone bipolar cells were clearly present, and with increasing age, two distinct strata of immunolabeled processes occupied the IPL. PKC-containing rod bipolar cells emerged by the fourth postnatal week and at this age have stratified arbors in the inner IPL. The early bias of bipolar axonal arbors in terminating in the inner or outer half of the IPL is confirmed by dye labeling of cells with somata in the inner nuclear layer. At P10, several days before ribbon synapses have been previously observed in the ferret IPL, the axon terminals of all dye-labeled bipolar cells were clearly stratified. The results suggest that bipolar cells could provide spatially localized interactions that are suitable for guiding dendritic lamination in the inner retina.

There are many levels of disorder in amblyopic vision, from basic acuity and contrast sensitivity loss to abnormal binocular vision and global perception of motion and form. Amblyopia treatment via patching to restore acuity often leaves other aspects of vision deficient. The source for these additional deficits is unclear. Neural correlates of poor binocular function and acuity loss are found in V1 and V2. However, they are generally not sufficient to account for behaviorally measured vision loss. This review summarizes the known cortical correlates of visual deficits found in association with amblyopia, particularly those relevant to binocular vision and higher-order visual processing, in striate and extrastriate cortex. Recommendations for future research address open questions on the role of suppression and oculomotor abnormalities in amblyopic vision, and underexplored mechanisms such as top-down influences on information transmission in the amblyopic brain.

Much of what is currently known about the visual response of retinal bipolar cells is based on studies of rod-dominant responses to flashes in the dark in the isolated retina. This minireview summarizes quantitative findings on contrast processing in the intact light-adapted retina based on intracellular recording from more than 400 cone-driven bipolar cells in the tiger salamander: 1) In the main, the contrast responses of ON and OFF cells are surprisingly similar, suggesting a need to refine the view that ON and OFF cells provide the selective substrates for processing of positive and negative contrasts, respectively. 2) Overall, the response is quite nonlinear, showing very high gain for small contrasts, some 10–15 times greater than that of cones, but then quickly approaches saturation for higher contrasts. 3) Under optimal conditions of light adaptation, both classes of bipolar cells show evidence for efficient coding with respect to the contrasts in natural images. 4) There is a marked diversity within both the ON and OFF bipolar cell populations and an absence of discrete subtypes. The dynamic ranges bracket the range of contrasts in nature. 5) For both ON and OFF cells, the receptive field organization shows a striking symmetry between center and surround for responses of the same polarity and thus opposite contrast polarities. 6) The latency difference between ON and OFF cells is about 30 ms, which seems qualitatively consistent with a delay due to the G-protein cascade in ON bipolar cells. 7) In sum, we report quantitative evidence for at least 11 transformations in signal processing that occur between the voltage response of cones and the voltage response of bipolar cells.

We have previously demonstrated that the neonatal rabbit retina contains a larger complement of cells that accumulate [3H]-GABA than does the adult. In order for these neurons to be classified as GABAergic, they must also contain endogenous GABA. We now report that these same neonatal cell populations are also immunoreactive to GABA antisera. In frozen sections from rabbit retina, treated with GABA antisera, immunoreactive processes in both synaptic layers were observed at postnatal day 1. The appearance of immunofluorescent fibers precedes that of photoreceptor and bipolar cell terminals in the outer plexiform layer and is diminished by postnatal day 5. Also noted, was a 50% decrease in the density of GABA-immunoreactive cell bodies in the inner nuclear and ganglion cell layers, accompanied by an increase in cell volume and a shift toward a more spherical cell shape of the remaining cells. At postnatal day 1 and 3, we also observed immunoreactive cells having the characteristic morphology of interplexiform cells. This cell type sends branches to both the outer and inner plexiform layers, thus a morphological basis for communication between the two developing plexiform layers is present as early as postnatal day 1. Thus, retinas from neonatal rabbits have a larger complement of cells that stain for endogenous GABA than does the adult. These results coupled with our previous studies suggest that GABAergic properties are expressed by a larger number of cell types in the neonate than in the adult and are consistent with the general hypothesis that GABA functions as a trophic agent during development.

Antibody labeling of the calcium-binding protein calbindin 28kD (CaBP) and gamma-aminobutyric acid (GABA) is altered by short-term monocular deprivation in the lateral geniculate nucleus and visual cortex of adult primates. It is not known whether these alterations occur in other subcortical visual structures. We therefore have examined antibody labeling to CaBP and GABA in the superior colliculus (SC) of visually deprived Rhesus monkeys. One group was monocularly enucleated as adults. The other monkeys experienced different types of monocular and binocular deprivation from birth, including occlusion of one eye, and/or surgically induced aphakia, optically corrected with extended-wear contact lenses, or an intraocular lens implant. Some of these monkeys also had one eye enucleated prior to perfusion.

In the SC of normal monkeys, CaBP-immunoreactive neurons formed three laminar tiers within SC, one within the zonal layer (ZL) and upper superficial gray layer (SGL), another bridging the optic and intermediate gray layers, and a third within the deep gray layer. CaBP neurons within the upper tier had small pyriform or stellate morphologies while those in the deeper tiers were slightly larger neurons, most with a stellate morphology. GABA-immunoreactive neurons were densely distributed within the SGL and more sparsely distributed within the deeper layers. These cells were mostly small neurons with horizontal, pyriform, or stellate morphologies.

Neither monocular enucleation nor occlusion nor aphakia combined with continuous occlusion of the fellow eye produced any visible reduction in antibody labeling in cells or neuropil within the SC. Full-field measures of labeling intensity (optical density) within the ZL and upper SGL revealed no consistent differences between the SC contralateral or ipsilateral to the affected eye in either CaBP- or GABA-labeled sections. Measures of the optical density, number, and size of labeled neurons also showed no consistent effects of enucleation and/or occlusion. We therefore conclude that the retino-geniculostriate and retino-collicular systems differ in their response to deprivation which is likely due to the significant overlap of retinal axons from the two eyes that occurs in the SC of the Rhesus monkey.

We report on the existence of lagged Y (YL) cells in the A laminae of the cat lateral geniculate nucleus (LGN) and on criteria for identifying them using visual and electrical stimulation. Like the lagged X (XL) cells described previously (Mastronarde, 1987a; Humphrey & Weller, 1988a), YL cells responded to a spot stimulus with an initial dip in firing and a delayed latency to discharge after spot onset, and an anomalously prolonged firing after spot offset. However, the cells received excitatory input from retinal Y rather than X afferents, and showed nonlinear spatial summation and other Y-like receptive-field properties. Three YL cells tested for antidromic activation from visual cortex were found to be relay cells, with long conduction latencies similar to those of XL cells.

Simultaneous recordings of a YL cell and its retinal Y afferents show striking parallels between lagged X and Y cells in retinogeniculate functional connectivity, and suggest that the YL-cell response profile reflects inhibitory processes occurring within the LGN. The YL cells comprised -5% of Y cells and -1% of all cells in the A laminae. Although infrequently encountered in the LGN, they may be roughly as numerous as Y cells in the retina, and hence could fulfill an important role in vision.

GABA receptor antagonists produce an unexpectedly significant inhibition of native glycine receptors in retina and in α1 or α2 homomeric glycine receptors (GlyRs) expressed in HEK 293 cells. In this study we evaluate this phenomenon in heteromeric glycine receptors, formed by mixing α1, α2, and β subunits. Picrotoxinin, picrotin, SR95531, and bicuculline are all more effective antagonists at GlyRs containing α2 subunits than α1 subunits. Inclusion of β subunits reduces the inhibitory potency of picrotoxinin and picrotin but increases the potency of SR95531 and bicuculline. As a result of these two factors, bicuculline is particularly poor at discriminating GABA and glycine receptors. Picrotin, which has been reported to be inactive at GABA receptors, blocks glycine currents in retina and in HEK293 cells, suggesting its utility as a selective glycine antagonist. However, picrotin is a more potent inhibitor of GABA than glycine in retinal neurons. We also tested if GABA and glycine receptor subunits can combine to form functional receptors. If GABAAR γ2S subunits are co-expressed with GlyR α subunits, the mixed receptor is glycine-sensitive and GABA-insensitive. But the mixed receptor exhibits a non-competitive picrotoxinin inhibition that is not observed in the homomeric GlyRs. This suggests that glycine and GABA subunits can co-assemble to form functional glycine receptors.

Cell responses to drifting Cartesian (parallel) and non-Cartesian (concentric, radial, and hyperbolic) stimuli were recorded in and beyond the classical receptive field (CRF) in the lateral geniculate nucleus (LGN), V1, and V2 of anesthetized monkeys. Many cells were equally responsive to Cartesian and non-Cartesian, especially concentric, gratings. Around 15% of cells in each area were significantly more responsive to concentric compared to parallel gratings; however, cells significantly more responsive to parallel compared to concentric gratings were more numerous in the cortex. While many cells responded to hyperbolic and radial gratings, few were most responsive to these gratings. Cell selectivity decreased for Cartesian and increased for non-Cartesian gratings from V1 to V2 and the relative response varied as a function of stimulus extent with respect to the CRF. Complex, nonoriented, nondirectional cells with a low aspect ratio (AR) responded best to non-Cartesian gratings. These results cannot be fully explained using Gabor linear/energy models of simple and complex receptive fields (RFs) although such models predict some cells to respond equally to Cartesian and non-Cartesian gratings. Cells significantly more responsive to non-Cartesian gratings can be accounted for by CRF selectivity influenced by modulation from the nonclassical receptive field (nCRF). The present study shows that Cartesian/non-Cartesian selectivity is not an emergent property of V4 cells but is present at all levels of early visual processing being subserved by a subset of cells with specific tuning properties.

There are several different groups of ganglion cells in the retina of the frog. Although their axons are thought to terminate in different layers of the optic tectum, little is known about the morphology of their terminal arbors or their synaptic targets. The present paper reports the results of a layer-by-layer study of horseradish peroxidase labeled retinal axons in the optic tectum of Rana pipiens. Light and electron microscopy was used to study the axon's laminar distribution, patterns of arborization, and synaptic contacts.

Labeled retinal axons were found in all of the superficial layers of the tectum (A-G). From layer to layer, the retinal axons differed markedly in the diameter of their parent axons (0.2−3.0 μm) and in the morphology and horizontal extent of their terminal arbors.

Five classes of synaptic terminals could be distinguished in the tectum. The retinal terminals belonged to class characterized by round, medium-sized synaptic vesicles. They made synaptic contact with dendrites and other axon terminals in each of the layers. They were always the presynaptic component. The postsynaptic dendrites were often the vertically oriented processes of cells located in the deeper layers. The postsynaptic terminals belonged to a class distinguished by their flat, medium-sized vesicles. These terminals in turn contacted what appeared to be dendrites. In layer eight, the retinal axons were often large, spoon-shaped boutons that ended in apposition with the somata of the layer.

Sharp electrodes were used to record light-evoked postsynaptic potentials (PSPs) from neurons in turtle visual cortex in an in vitro preparation of the geniculocortical pathway. Neurons were placed into four groups based on the firing patterns produced by intracellular current injections: regular spiking (RS), fast spiking (FS), intrinsic bursting (IB), and chattering (CH) cells. RS cells have been shown to be pyramidal cells while FS cells are typically interneurons. Light stimuli were diffuse, 1-s flashes of 640-nm light with intensities (I) varying from 0 to 104 photons μm−2 s−1. The response (R) in each case was the maximal amplitude of the light-evoked depolarizing PSP. Cells of all four types showed sigmoidal intensity–response (IR) functions with a linear rising phase for stimuli above the intensity threshold followed by saturation at high light intensities. Responses at high intensities were variable and some cells showed indications of supersaturation. Light-evoked PSPs had longer latencies and times-to-peak response in RS cells than they did in FS cells. RS cells fired action potentials as much as 200 ms later than did FS cells. Since responses recorded in RS cells at light intensities just above threshold are unlikely to involve contributions from other pyramidal cells, these data indicate that the geniculocortical or feedforward pathway to pyramidal cells has a high gain. The fact that FS cells fire well before RS cells suggests that feedforward inhibition plays a role in controlling the gain of the geniculocortical pathway.

The spectral sensitivity of cones in isolated goldfish retina was determined with whole-cell recording techniques. Three spectral classes of cones were found with maximal sensitivities around 620 nm, 540 nm, and 460 nm. UV-cones were not found because our stimulator did not allow effective stimulation in the UV range. The spectral sensitivity of the cones closely matched the cone photopigment absorption spectra at the long wavelength side of the spectrum, but deviated significantly at shorter wavelengths. Surround stimulation induced an inward current in cones due to feedback from horizontal cells. The spectral sensitivity of this feedback signal was determined in all three cone classes and found to be broader than the spectral sensitivity of the cones recorded from, and to be spectrally nonopponent. These data are consistent with a connectivity scheme between cones and horizontal cells in which the three horizontal cell systems feed back to all cone systems and in which all horizontal cell systems receive input from more than one cone system.

Spatial summation and degree of center-surround antagonism were examined in the receptive field of nonlagged cells in the dorsal lateral geniculate nucleus (dLGN). We recorded responses to stationary light or dark circular spots that were stepwise varied in width. The spots were centered on the receptive field. For a sample of nonlagged X-cells, we made simultaneous recordings of action potentials and S-potentials, and could thereby compare spatial summation in the dLGN cell and in the retinal input to the cell. Plots of response versus spot diameter showed that the response for a dLGN cell was consistently below the response in the retinal input at all spot sizes. There was a marked increase of antagonism at the retinogeniculate relay. The difference between the retinal input and dLGN cell response suggested that the direct retinal input to a relay cell is counteracted in dLGN by an inhibitory field that has an antagonistic center-surround organization. The inhibitory field seems to have the same center sign (ON- or OFF-center), but a wider receptive-field center than the direct retinal input to the relay cell. The broader center of the inhibitory field can explain the increased center-surround antagonism at the retinogeniculate relay. The ratio between the response of a dLGN cell and its retinal input (transfer ratio) varied with spot width. This variation did not necessarily reflect a nonlinearity at the retinogeniculate relay. Plots of dLGN cell response against retinal input were piecewise linear, suggesting that both excitatory and inhibitory transmission in dLGN are close to linear. The variation in transfer ratio could be explained by sustained suppression evoked by the background stimulation, because such suppression has relatively stronger effect on the response to a spot evoking weak response than to a spot evoking a strong response. A simple model for the spatial receptive-field organization of nonlagged X-cells, that is consistent with our findings, is presented.

Simple color-difference formulae and pictorial images have traditionally been used to estimate the visual impact of color errors introduced by image-reproduction processes. But the limited gamut of RGB cameras constrains such analyses, particularly of natural scenes. The purpose of this work was to estimate visual sensitivity to color errors introduced deliberately into pictures synthesized from hyperspectral images of natural scenes without gamut constraints and to compare discrimination thresholds expressed in CIELAB and S-CIELAB color spaces. From each original image, a set of approximate images with variable color errors were generated and displayed on a calibrated RGB color monitor. The threshold for perceptibility of the errors was determined in a paired-comparison experiment. In agreement with previous studies, it was found that discrimination between original and approximate images needed on average a CIELAB color difference ΔEab* of about 2.2. Although a large variation of performance across the nine images tested was found when errors were expressed in CIELAB units, little variation was obtained when they were expressed in S-CIELAB units.

In the kitten, as little as a week of monocular lid suture during early life causes a remarkable remodeling of the geniculocortical projections serving the deprived eye (Antonini & Stryker, 1993a, 1996). While the physiological effects of monocular deprivation have been shown to be due to competitive interactions between the projections serving the two eyes, it is not known whether these morphological changes are due to competitive interactions or to sensory disuse. We addressed this question by analyzing the morphology of geniculocortical arbors in kittens deprived of patterned vision by binocular lid suture for 1 week or 2 weeks ending at 6 weeks of age. Such deprivation would be expected to affect the afferents serving the two eyes equally, giving neither eye a competitive advantage. The arbors were anterogradely filled with Phaseolus lectin iontophoretically injected into lamina A of the lateral geniculate nucleus. The lectin was visualized immunohistochemically, and single geniculocortical arbors were serially reconstructed in three dimensions. Arbors reconstructed in binocularly deprived animals were compared with arbors serving the deprived and nondeprived eye in animals monocularly deprived by lid suture of one eye for a week and with arbors obtained in age-matched normal controls. Geniculocortical arbors in binocularly deprived animals did not suffer the drastic remodeling of the deprived arbors in monocularly deprived animals. Indeed, arbors in binocularly deprived animals were indistinguishable from arbors in normal kittens or nondeprived arbors in short-term monocularly deprived animals. These results support the notion that competitive mechanisms rather than sensory disuse are responsible for gross morphological remodeling of geniculocortical arbors.

In goldfish, negative feedback from horizontal cells to cones shifts the activation function of the Ca2+ current of the cones to more negative potentials. This shift increases the amount of Ca2+ flowing into the cones, resulting in an increase in glutamate release. The increased glutamate release forms the basis of the feedback-mediated responses in second-order neurons, such as the surround-induced responses of bipolar cells and the spectral coding of horizontal cells. Low concentrations of Co2+ block these feedback-mediated responses in turtle retina. The mechanism by which this is accomplished is unknown. We studied the effects of Co2+ on the cone/horizontal network of goldfish retina and found that Co2+ greatly reduced the feedback-mediated responses in both cones and horizontal cells in a GABA-independent way. The reduction of the feedback-mediated responses is accompanied by a small shift of the Ca2+ current of the cones to positive potentials. We have previously shown that hemichannels on the tips of the horizontal cell dendrites are involved in the modulation of the Ca2+ current in cones. Both the absence of this Co2+-induced shift of the Ca2+ current in the absence of a hemichannel conductance and the sensitivity of Cx26 hemichannels to low concentrations of Co2+ are consistent with a role for hemichannels in negative feedback from horizontal cells to cones.

Layers II/III of the primary visual cortex contain a regular pattern of histochemically detectable cytochrome oxidase (CO)-rich “puffs,” which differ from the interpuff regions in their thalamo-cortical and cortico-cortical connectivity, receptive-field properties, and the density of inhibitory GABA-containing synaptic terminals. We used an immunocytochemical method, in combination with cytochrome oxidase histochemistry, to analyze the spatial relationship between neurons that contain neuropeptide Y (NPY) and the CO puffs. Of a total of 606 neurons, only 2.6% of the NPY-containing cells are located in the puffs, whereas the rest are situated in the interpuffs, or at the interface between puffs and interpuffs. The number of NPY-containing neurons in the puffs is substantially less than that expected in an equal volume of the interpuffs (X2 = 13.86; df = 1; P < 0.001).

These observations indicate that columns containing the puffs may differ also from those in the interpuff regions in that they contain a unique array of chemically and morphologically distinct local circuit neurons.

Neurons in the nucleus praetectalis olivaris (NPO) were antidromically identified by electrical stimulation of the nucleus of Edinger-Westphal (EW), the location of preganglionic pupilloconstrictor motoneurons. Electrical stimulation within the NPO leads to bilateral pupil constriction. Single neurons recorded in the NPO respond tonically to light stimuli, and their discharge frequency increases linearly with logarithmic increase in light intensity. This characteristic identifies NPO neurons as luminance detectors. They have large receptive fields mostly lying in the upper and contralateral quadrant of the visual field.

Cats with impaired binocular vision show a significantly reduced binocular summation of the pupillary light reflex (BSP), i.e. the increase of pupil constriction during binocular illumination when compared to monocular illumination is less than in normal animals. The investigation of ocular dominance and subthreshold binocular interactions in the NPO of normal and innate microstrabismic cats revealed two possible mechanisms for BSP and its reduction in strabismic subjects. First, the percentage of neurons increasing their discharge rate by illuminating either eye is significantly reduced in the NPO of innate microstrabismic cats (6.6%) when compared to normal cats (22% of all neurons tested). Second, in most NPO neurons of normal cats the subthreshold influence of the ipsilateral eye leads to an increase in neuronal activity during binocular stimulation when compared to monocular stimulation of the contralateral eye (binocular summation). The subthreshold influence of the ipsilateral eye in most NPO neurons of microstrabismic cats, however, is inhibitory, i.e. the neuronal discharge rate during binocular stimulation is decreased when compared to monocular stimulation of the contralateral eye (binocular inhibition). However, there is no significant correlation between BSP and binocularity in the NPO in individual animals. This suggests that BSP may be additionally influenced by visual structures other than NPO.

Electrical coupling of photoreceptors through gap junctions suppresses voltage noise, routes rod signals into cone pathways, expands the dynamic range of rod photoreceptors in high scotopic and mesopic illumination, and improves detection of contrast and small stimuli. In essentially all vertebrates, connexin 35/36 (gene homologs Cx36 in mammals, Cx35 in other vertebrates) is the major gap junction protein observed in photoreceptors, mediating rod–cone, cone–cone, and possibly rod–rod communication. Photoreceptor coupling is dynamically controlled by the day/night cycle and light/dark adaptation, and is directly correlated with phosphorylation of Cx35/36 at two sites, serine110 and serine 276/293 (homologous sites in teleost fish and mammals, respectively). Activity of protein kinase A (PKA) plays a key role during this process. Previous studies have shown that activation of dopamine D4 receptors on photoreceptors inhibits adenylyl cyclase, down-regulates cAMP and PKA activity, and leads to photoreceptor uncoupling, imposing the daytime/light condition. In this study, we explored the role of adenosine, a nighttime signal with a high extracellular concentration at night and a low concentration in the day, in regulating photoreceptor coupling by examining photoreceptor Cx35 phosphorylation in zebrafish retina. Adenosine enhanced photoreceptor Cx35 phosphorylation in daytime, but with a complex dose–response curve. Selective pharmacological manipulations revealed that adenosine A2a receptors provide a potent positive drive to phosphorylate photoreceptor Cx35 under the influence of endogenous adenosine at night. A2a receptors can be activated in the daytime as well by micromolar exogenous adenosine. However, the higher affinity adenosine A1 receptors are also present and have an antagonistic though less potent effect. Thus, the nighttime/darkness signal adenosine provides a net positive drive on Cx35 phosphorylation at night, working in opposition to dopamine to regulate photoreceptor coupling via a push–pull mechanism. However, the lower concentration of adenosine present in the daytime actually reinforces the dopamine signal through action on the A1 receptor.