Light responses of R/G chromaticity-type horizontal cells (R/G HCs) and luminosity-type horizontal cells (LHCs) were intracellularly recorded in isolated superfused carp retina, and the response dynamics analyzed. The results revealed that (1) No significant difference in delay was detected between R/G HC red and green responses; (2) The rising speed was quicker for R/G HC depolarizing red responses compared to that of its hyperpolarizing green responses; and (3) Dynamic characteristics of R/G HC red responses and its changes caused by green background illumination did not follow that of LHC red response. All these results suggest that the depolarizing response of the R/G HCs cannot be entirely mediated by the negative feedback pathway from LHCs onto cones. A direct inhibitory input from red cones to R/G HCs may exist.

The thalamus is the major gate to the cortex and its control over cortical responses is well established. Cortical feedback to the thalamus is, in turn, the anatomically dominant input to relay cells, yet its influence on thalamic processing has been difficult to interpret. For an understanding of complex sensory processing, detailed concepts of the corticothalamic interplay need yet to be established. Drawing on various physiological and anatomical data, we elaborate the novel hypothesis that the visual cortex controls the spatiotemporal structure of cortical receptive fields via feedback to the lateral geniculate nucleus. Furthermore, we present and analyze a model of corticogeniculate loops that implements this control, and exhibit its ability of object segmentation by statistical motion analysis in the visual field.

A model is presented for the early (retinal) stages of temporal processing of light inputs in the visual system. The model consists of a sequence of three adaptation processes, with two instantaneous nonlinearities in between. The three adaptation processes are, in order of processing of the light input: a divisive light adaptation, a subtractive light adaptation, and a contrast gain control. Divisive light adaptation is modeled by two gain controls. The first of these is a fast feedback loop with square-root behavior, the second a slow feedback loop with logarithm-like behavior. This can explain several aspects of the temporal behavior of photoreceptor outputs. Subtractive light adaptation is modeled by a high-pass filter equivalent to a fractional differentiation, and it can explain the attenuation of low frequencies observed in ganglion cell responses. Contrast gain control in the model is fast (Victor, 1987), and can explain the decreased detectability of test signals that are superimposed on dynamic backgrounds. We determine psychophysical detection thresholds for brief test pulses that are presented on flickering backgrounds, for a wide range of temporal modulation frequencies of these backgrounds. The model can explain the psychophysical data for the full range of modulation frequencies tested, as well as detection thresholds obtained for test pulses on backgrounds with increment and decrement steps in intensity.

It has been observed that deep-foraging marine mammals have visual pigments that are blue shifted in terms of their wavelength of maximal absorbance (λmax) when compared to analogous pigments from terrestrial mammals. The mechanisms underlying the spectral tuning of two of these blue-shifted pigments have recently been elucidated and depend on three amino acid substitutions (83Asn, 292Ser, and 299Ser) in dolphin rhodopsin, but only one amino acid substitution (308Ser) in the dolphin long-wavelength-sensitive pigment. The objective of this study was to investigate the molecular basis for changes in the spectral sensitivity of rod visual pigments from seven distantly related marine mammals. The results show a relationship between blue-shifted rhodopsins (λmax ≤ 490 nm), deep-diving foraging behavior, and the substitutions 83Asn and 292Ser. Species that forage primarily near the surface in coastal habitats have a rhodopsin with a λmax similar to that of terrestrial mammals (500 nm) and possess the substitutions 83Asp and 292Ala, identical to rhodopsins from terrestrial mammals.

Adult teleost fish retinas can regenerate neurons following either surgical or pharmacological injury. The cellular milieu of the damaged retina within which regenerated neurons are produced might be different in these two model systems of retinal injury, and thus the phenotypic attributes of regenerated neurons in the two model systems might also differ. To determine if the phenotypic attributes of photoreceptors, and by extension the recovery of vision, are different between these two model systems, we compared the visual pigment content and morphology of photoreceptors derived from goldfish retinas of both models with control retina. Visual pigments—which consist of a protein moiety (opsin) and a chromophore—were analyzed in single, isolated photoreceptors using microspectrophotometric techniques. We report that visual pigments and photoreceptor morphologies in the surgical model closely matched those of native retina. In contrast, neither photoreceptor morphology nor visual pigment content matched closely in the pharmacological model. The results indicate that phenotypic attributes of photoreceptors can differ significantly between the two model systems of retinal regeneration, but that in both systems, rod- and cone-mediated visual functions can potentially be reestablished.

One type of retinal ganglion cells prefers object motion in a particular direction. Neuronal mechanisms for the computation of motion direction are still unknown. We quantitatively mapped excitatory and inhibitory regions of receptive fields for directionally selective retinal ganglion cells in the Japanese quail, and found that the inhibitory regions are displaced about 1–3 deg toward the side where the null sweep starts, relative to the excitatory regions. Directional selectivity thus results from delayed transient suppression exerted by the nonconcentrically arranged inhibitory regions, and not by local directional inhibition as hypothesized by Barlow and Levick (1965).

Psychophysical (behavioral) detection thresholds and color-discrimination thresholds were determined in a macaque using a two-alternative forced-choice procedure. On a white background, detection thresholds were determined for a white increment and three spectral increments: 618, 516, and 456 nm. Intermixed with detection threshold determinations, color-discrimination thresholds were determined by presenting the white increment, and one of the spectral increments, at 1.0 log units above their respective detection thresholds and dimming both until discrimination performance fell to threshold. The monkey could discriminate the color of the increments at detection threshold because the average color-discrimination threshold was 0.98 ± 0.14 log attenuation. Because the monkey was much more sensitive to the spectral increments than the white increment, we performed an unconventional experiment. We determined the monkey's detection threshold for the white increment alone, and with broadband color filters in the white light path without adjusting the light's intensity. Insertion of several color filters in the light path lowered detection thresholds of both the macaque and six human trichromats. We believe that this improvement in detection thresholds produced by simply inserting color filters in a white light path is a threshold manifestation of the Helmholtz-Kohlrausch effect and suggests that one of color vision's important evolutionary advantages may be improved detection sensitivity.

Gamma aminobutyric acid (GABA) has been established as an important developmental signal in a number of regions of the central nervous system (CNS), including retina. Our previous studies have shown that GABAergic horizontal cells act as the initial synaptic target for developing cone photoreceptors in neonatal rabbit retina. Since intraocular injections of the GABAA receptor antagonists, picrotoxin or bicuculline, disrupt cone synaptogenesis in vivo, GABA released from horizontal cells may provide a necessary signal for cone axon growth and/or synapse formation. In the current report, we have used cultured retinal explants to examine the effects of GABAA receptor antagonists on other aspects of developing cones. These include the distribution pattern of cone cell bodies across the outer surface of the retina and the expression of GABAA receptors within both cone cell bodies and axonal processes. Peanut agglutinin (PNA), a plant lectin that specifically labels cone plasma membrane and extracellular matrix, was used to monitor cone development, and a GABAA receptor antibody against the β2/3 subunits of the protein was used to label GABAA receptors. Results showed that cones maintained in the explant culture express GABAA receptors in a temporal and spatial pattern similar to that observed in vivo, namely a low expression of receptors on cone cell bodies at postnatal day 1 (P1), peaking around P3 and diminishing by P7. Neonatal retinal explants exposed to the GABAA receptor antagonists, bicuculline (10 μM) or SR95531 (5 μM), for 24 h in culture showed disruption of the normal distribution of cone cell bodies. When GABA (100 μM) was added along with either antagonist, cone cell bodies appeared normal. Neither bicuculline nor SR95531 alone had any effect on the general morphology of other retinal layers, suggesting that these GABAA receptor antagonists at the concentrations used were not acting as nonspecific disruption agents. The effects of GABA antagonists were confined to the first week after birth with no disruption seen in P9 or adult explant cultures. These data provide a direct demonstration of the necessity for GABAergic input to cones during active synaptogenesis. As we have previously shown, GABAA receptor activation causes a substantial increase in intracellular calcium concentrations in cones and thereby could provide a mechanism by which GABA regulates cone maturation.

The retinas of adult teleost fish can regenerate neurons following a chemical or mechanical injury. Previous studies have demonstrated that mechanical excision of fish retina induces a hyperplasia within the retinal sheet, including the formation of a proliferative blastema from whence new retinal cells are produced to fill the excision site. The current study was designed to address two issues regarding injury-induced retinal hyperplasia: (1) Retinas of adult zebrafish can regenerate following a surgical excision, but compared to other fish they contain very few proliferative cells: Might retinal injury in adult zebrafish therefore induce minimal, or perhaps no, hyperplasia? (2) The fate of injury-induced, proliferative retinal cells outside surgical excision sites has yet to be determined. Do such cells produce retinal neurons? Evidence is presented that mechanical injury to the adult zebrafish retina induces a dramatic increase in the number of proliferative cells both within and external to the lesion site, and some of these cells apparently migrate within the radial dimension of the retina. Evidence is also presented that injury-induced proliferative cells outside a lesion site can produce retinal neurons—including cone photoreceptors, interplexiform cells, and amacrine cells—that are incorporated into the extant retina. The results suggest that the adult zebrafish retina contains a latent population of cells that is induced to proliferate following retinal injury, and that these cells might represent a novel avenue for pluripotent neurogenesis within the intact adult teleost retina.

This study reports Müller cell and neuronal changes and microglial reaction in streptozotocin-induced diabetic rats. Glial fibrillary acidic protein (GFAP) immunoreactivity was largely confined to astrocytes in the nerve fiber layer (NFL) and ganglion cell layer (GCL) in control rats. In diabetic rats especially those killed after 12 months, GFAP immunostaining could be traced along the entire length of Müller cell processes, extending from the inner to the outer limiting membrane. With the antibody neuronal nuclei, immunopositive cells were located in the GCL and the inner part of the inner nuclear layer (INL) in both diabetic and age-matched control rats. In diabetic rats, labelled cells were reduced in both layers being more marked in the INL. In age-matched control rats, OX42-immunoreactive microglial cells were distributed mainly in the NFL and GCL; some cells were localized in the inner plexiform layer, but rarely in the outer plexiform layer (OPL). Beginning 1 month after diabetes, the microglial cells appeared hypertrophic. Furthermore, microglial number as estimated from cell counts in different layers of the retina was significantly increased, with the occurrence of some cells in the OPL at 4 months. At 14 and 16 months, reactive microglial cells were detected in the outer nuclear layer and photoreceptor layer. Present results suggest that microglial reaction in induced diabetes was elicited by neuronal cell loss in both GCL and INL as well as by some pathologic changes affecting the photoreceptors.

Mechanisms of motion vision in the human have been studied extensively by psychophysical methods but less frequently by electrophysiological techniques. It is the purpose of the present investigation to study electrical potentials of the eye (electroretinogram, ERG) and of the brain (visual evoked potential, VEP) in response to moving regular square-wave stripe patterns spanning a wide range of contrasts, spatial frequencies, and speeds. The results show that ERG amplitudes increase linearly with contrast while VEPs, in agreement with the literature, show an amplitude saturation at low contrast. Furthermore, retinal responses oscillate with the fundamental temporal stimulus frequency of the moving pattern while brain responses do not. In both the retina and the brain, the response amplitudes are tuned to certain speeds which is in agreement with the nonlinear correlation-type motion detector. Along the ascending slopes (which means increasing amplitudes) of the tuning functions, the ERG curves overlap at all spatial frequencies if plotted as a function of temporal stimulation frequency. The ascending slopes of the tuning functions of the VEP overlap if plotted as a function of speed. The descending slopes (which means decreasing amplitudes) of the tuning functions show little (ERG) or no (VEP) overlap and the waveforms at high speeds approach pattern-offset-onset responses. These observations suggest that in the retina motion processing along the ascending slopes of the tuning curves takes place by coding the temporal stimulation frequency which depends on the spatial frequency of the moving pattern. In the brain, however, motion processing is by speed independent of spatial frequency. Simple calculations show that the VEP information is decoded from the ERG signal into a speed signal.

The localization of endogenous Zn2+ in the mouse retina was examined histochemically and the inhibitory action of Zn2+ on GABA-induced responses was studied in bipolar cells isolated from the mouse retina. Accumulation of endogenous Zn2+ was detected in photoreceptors, bipolar, and/or amacrine cells by either the bromopyridylazo-diethylaminophenol method or the dithizone method. Under whole-cell recording conditions, GABA induced a Cl− current in isolated bipolar cells. The current consisted of two components. The first component was inhibited completely by application of 100 μM bicuculline, suggesting that this is a GABAA-receptor mediated current. The second component was inhibited completely by 100 μM 3-aminopropyl-(methyl)-phosphinic acid, suggesting that this is a GABAC-receptor mediated current. GABAC receptors were present at a higher density on the axon terminal than on dendrites. Zn2+ inhibited both GABAA and GABAC receptors. GABAC receptors were more susceptible to Zn2+; the IC50 for the GABAA receptor was 67.4 μM and that for the GABAC receptor was 1.9 μM. These results suggest that Zn2+ modulates the inhibitory interaction between amacrine and bipolar cells, particularly that mediated by the GABAC receptor.

The retinae of insectivores have been rarely studied, and their photoreceptor arrangements and expression patterns of visual pigments are largely unknown. We have determined the presence and distribution of cones in three species of shrews (common shrew Sorex araneus, greater white-toothed shrew Crocidura russula, dark forest shrew Crocidura poensis; Soricidae) and in the lesser hedgehog tenrec Echinops telfairi (Tenrecidae). Spectral cone types were identified and quantified in flattened whole retinae by antisera/antibodies recognizing the middle-to-long-wavelength-sensitive (M/L-)cone opsin and the short-wavelength-sensitive (S-)cone opsin, respectively. A combination of immunocytochemistry with conventional histology was used to assess rod densities and cone/rod ratios. In all four species the rods dominate at densities of about 230,000–260,000/mm2. M/L- and S-cones are present, comprising between 2% of the photoreceptors in the nocturnal Echinops telfairi and 13% in Sorex araneus that has equal diurnal and nocturnal activity phases. This suggests dichromatic color vision like in many other mammals. A striking feature in all four species are dramatically higher S-cone proportions in ventral than in dorsal retina (0.5% vs. 2.5–12% in Sorex, 5–15% vs. 30–45% in Crocidura poensis, 3–12% vs. 20–50% in Crocidura russula, 10–30% vs. 40–70% in Echinops). The functional and comparative aspects of these structural findings are discussed.

Retinal horizontal cells display large receptive fields as a result of extensive electrical coupling via gap junctions. There is abundant evidence that these gap junctions are dynamically regulated by changes in the adaptational state of the retina. The neuromodulator dopamine appears to play a major role in regulating gap junctional conductances of horizontal cells. Emerging evidence indicates that nitric oxide (NO) also acts as a neuromodulator in the retina and, more specifically, regulates the coupling between horizontal cells. In the present study, we examined the effects of a nitric oxide, and its secondary messenger cGMP, on electrical and tracer coupling between A-type and between B-type horizontal cells in the rabbit retina. Application of the NO donors S-nitroso-N-acetylpenicillamine (SNAP) or sodium nitroprusside (SNP) significantly reduced the coupling between horizontal cells as evidenced by a decrease in their space constants, annulus-to-small spot response ratios, and the extent of tracer coupling following injection with Neurobiotin. Further, application of SNP eliminated the increase in coupling of horizontal cells normally seen with exposure to dim background illumination. Application of 8-bromo-cGMP produced effects similar to those of the NO donors, consistent with the idea that the uncoupling actions of NO were mediated via a cGMP cascade.

Although single-channel and whole-cell patch-clamp recordings have demonstrated the presence of Na+ currents in retinal ganglion cell somata, it has not previously been reported that an anti-Na+-channel antiserum stains both retinal ganglion cell somata and proteins with molecular weights corresponding to complexes of α and β subunits. We probed adult goldfish retinas for Na+ channel-like immunoreactivity with a polyclonal antibody directed against the EOIII segment of vertebrate voltage-gated Na+ channels. In vertical sections and whole mounts, this antibody consistently stained the somata, axons, and proximal dendrites of retinal ganglion cells. Some somata in the proximal third of the inner nuclear layer were also stained. In Western blots, this antibody specifically stained multiple protein bands from retina and optic nerve, all with apparent molecular weights between 200 and 315 kDa. The largest of these molecular weights agrees with that reported previously for complexes of α and β subunits in mammalian neurons, including retinal ganglion cells. The intermediate and lowest molecular weights are consistent with the presence of multiple Na+ channel α subunits, either in individual proximal retinal neurons or in different morphological subtypes.

In the rat, the superficial gray layer (SGS) of the superior colliculus receives glutamatergic projections from the contralateral retina and from the visual cortex. A few fibers from the ipsilateral retina also directly innervate the SGS, but most of the ipsilateral visual input is provided by cholinergic afferents from the opposing parabigeminal nucleus (PBG). Thus, visual input carried by cholinergic afferents may have a functional influence on the responses of SGS neurones. When single neuronal extracellular recording and iontophoretic drug application were employed to examine this possibility, cholinergic agonists were found to depress responses to visual stimulation. Lobeline and 1-acetyl-4-methylpiperazine both depressed visually evoked activity and had a tendency to reduce the background firing rate of the neurones. Carbachol depressed the visual responses without any significant effect on the ongoing activity, while the muscarinic receptor selective agonist methacholine increased the background activity of the neurones and reduced their visual responses. Lobeline was chosen for further studies on the role of nicotinic receptors in SGS. Given that nicotinic receptors are associated with retinal terminals in SGS, and that the activation of presynaptic nicotinic receptors normally facilitates transmitter release (in this case glutamate release), the depressant effects of nicotinic agonists are intriguing. However, many retinal afferents contact inhibitory neurones in SGS; thus it is possible that the increase in glutamate release in turn facilitates the liberation of GABA which goes on to inhibit the visual responses. We therefore attempted to reverse the effects of lobeline with GABA receptor antagonists. The depressant effects of lobeline on the visual response could not be reversed by the GABAA antagonist bicuculline, but the GABAB antagonist CGP 35348 reduced the effects of lobeline. We hypothesize that cholinergic drive from the parabigeminal nucleus may activate presynaptic nicotinic receptors on retinal terminals, thereby facilitating the release of glutamate onto inhibitory neurones. Consequently GABA is released, activating GABAB receptors, and thus the ultimate effect of nicotinic receptor activation is to depress visual responses.

Cephalopod retinas exhibit several responses to light and dark adaptation, including rhabdom size changes, photopigment movements, and pigment granule migration. Light- and dark-directed rearrangements of microfilament and microtubule cytoskeletal transport pathways could drive these changes. Recently, we localized actin-binding proteins in light-/dark-adapted octopus rhabdoms and suggested that actin cytoskeletal rearrangements bring about the formation and degradation of rhabdomere microvilli subsets. To determine if the microtubule cytoskeleton and associated motor proteins control the other light/dark changes, we used immunoblotting and immunocytochemical procedures to map the distribution of tubulin, kinesin, and dynein in dorsal and ventral halves of light- and dark-adapted octopus retinas. Immunoblots detected α- and β-tubulin, dynein intermediate chain, and kinesin heavy chain in extracts of whole retinas. Epifluorescence and confocal microscopy showed that the tubulin proteins were distributed throughout the retina with more immunoreactivity in retinas exposed to light. Kinesin localization was heavy in the pigment layer of light- and dark-adapted ventral retinas but was less prominent in the dorsal region. Dynein distribution also varied in dorsal and ventral retinas with more immunoreactivity in light- and dark-adapted ventral retinas and confocal microscopy emphasized the granular nature of this labeling. We suggest that light may regulate the distribution of microtubule cytoskeletal proteins in the octopus retina and that position, dorsal versus ventral, also influences the distribution of motor proteins. The microtubule cytoskeleton is most likely involved in pigment granule migration in the light and dark and with the movement of transport vesicles from the photoreceptor inner segments to the rhabdoms.

Catfish cone horizontal cells contain a voltage-gated L-type calcium channel that is modulated by activation of metabotropic glutamate receptors (mGluRs). Activation of group I mGluRs with the mGluR I agonist, (S)-3,5-dihydroxyphenylglycine [(S) 3,5-DHPG], potentiated peak calcium current amplitude, shifted the membrane potential corresponding to peak current activity, and widened the calcium current's activation range. In this study, we have examined the mechanisms linking activation of the mGluRs with “up-regulation” of calcium current activity. Under whole-cell voltage-clamp conditions favoring expression of the L-type calcium current, we provide evidence that activation of mGluRs initiate the diacylglyceral (DG) second messenger pathway to activate protein kinase C (PKC) and up-regulate calcium channel activity. This evidence was based on results using a number of PKC activators and inhibitors. PKC activators mimicked the effect of (S) 3,5-DHPG on calcium current activity. Up-regulation of the calcium channel by PKC activators or (S) 3,5-DHPG was eliminated if PKC inhibitors were present. These results also demonstrated that activation of group I mGluRs were linked to a pertussis toxin sensitive G-protein. When the GTP analog, guanosine 5-0-(3-thiotriphosphate (GTPγS), was allowed to diffuse into voltage-clamp cells, up-regulation of the calcium channel occurred and mimicked the effect of (S) 3,5-DHPG. However, when pertussis toxin (PTX) was allowed to diffuse into the cell along with GTPγS, GTPγS failed to modulate calcium current activity. IP3 (inositol 1,4,5 triphosphate) is a second product produced by activation of group I mGluRs. Once formed, IP3 can trigger calcium release from IP3-sensitive intracellular stores. To determine if the IP3 second messenger system was involved in up-regulation of calcium channel, (S) 3,5-DHPG was applied to voltage-clamped cone horizontal cells containing different concentrations of the calcium buffer, EGTA. Low concentrations of EGTA failed to buffer calcium released from intracellular stores. In the presence of low EGTA concentrations, (S) 3,5-DHPG's enhancement of the calcium current amplitude was reduced. Inhibition of the calcium current amplitude in low concentrations of EGTA was eliminated in the presence of the intracellular calcium store blocker, heparin. These results suggest that both the DG and IP3 second messenger pathways are involved in modulation of the voltage-gated calcium channel in catfish cone horizontal cells. The DG pathway up-regulates the voltage-gated calcium channel activity whereas calcium released from IP3 intracellular stores inhibits peak current amplitude.

This study examined the question of which features of a complex grouping discrimination make it vulnerable to permanent elimination by V4 lesions. We first verified that the line element grouping discrimination, which we previously reported to be devastated by V4 lesions, was similarly affected in the monkeys of this study. The permanence of the deficit was established by mapping its visual field distribution and then testing this discrimination for an extended period at a locus on the border of the deficit. Also, a staircase procedure was used to provide the monkey with within session instruction in the grouping discrimination, but this did not improve V4 lesion performance. Grouping was then compared with several discriminations that shared some features with it, but which were found not to be permanently eliminated by V4 lesions. This comparison suggested that grouping (rather than segmentation or response to a single element) was one feature that made the discrimination vulnerable, a second was the similarity in shape of the texture elements to be grouped. Finally, we tested visual crowding, a property of peripheral vision that is thought to reflect neuronal interactions early in visual cortex, possibly in area V1, and found no effect of V4 lesions. A control experiment with human observers tested whether the elimination of grouping by V4 lesions might be due to an alteration of attention, but found no evidence to support this hypothesis. These results show that severe disruption of texture discriminations by V4 lesions depends on both the nature of the discrimination and the type of texture elements involved, but does not necessarily involve the disruption of attention.

Due to technical difficulties that have since been rectified, the photomicrographs in this article did not reproduce at the best resolution possible. Also, Figure 12 has been revised and a corrected version of the article is reproduced on pp. 1R–9R, which follows. Cambridge University Press regrets any inconvenience that this inadvertent error may have caused.