Signals relayed through the magnocellular layers of the LGN travel on axons with faster conduction speeds than those relayed through the parvocellular layers. As a result, magnocellular signals might reach cerebral cortex appreciably before parvocellular signals. The relative speed of these two channels cannot be accurately predicted based solely on axon conduction speeds, however. Other factors, such as different degrees of convergence in the magnocellular and parvocellular channels and the retinal circuits that feed them, can affect the time it takes for magnocellular and parvocellular signals to activate cortical neurons. We have investigated the relative timing of visual responses mediated by the magnocellular and parvocellular channels. We recorded individually from 78 magnocellular and 80 parvocellular neurons in the LGN of two anesthetized monkeys. Visual response latencies were measured for small spots of light of various intensities. Over a wide range of stimulus intensities the fastest magnocellular response latencies preceded the fastest parvocellular response latencies by about 10 ms. Because parvocellular neurons are far more numerous than magnocellular neurons, convergence in cortex could reduce the magnocellular advantage by allowing parvocellular signals to generate detectable responses sooner than expected based on the responses of individual parvocellular neurons. An analysis based on a simple model using neurophysiological data collected from the LGN shows that convergence in cortex could eliminate or reverse the magnocellular advantage. This observation calls into question inferences that have been made about ordinal relationships of neurons based on timing of responses.

We studied the effects of contextual modulation in area V1 of anesthetized macaque monkeys. In 146 cells, responses to a single line over the center of the receptive field were compared with those to full texture patterns in which the center line was surrounded by similar lines at either the same orientation (uniform texture) or the orthogonal orientation (orientation contrast). On average, the responses to single lines were reduced by 42% when texture was presented in the surround. Uniform textures often produced stronger suppression (7% more, on average) so that lines with orientation contrast on average evoked larger responses than lines in uniform texture fields. This difference is correlated with perceptual differences between such stimuli, suggesting that physiological mechanisms contributing to the saliency (“popout”) of textural stimuli operate, at least to some degree, even under anesthesia. Significant response modulation by the texture surround was seen in 112 cells (77%). Fifty-three cells (36%) responded differently to the two texture patterns; response preferences for orientation contrast (35 cells; 24%) were seen more often than preferences for uniform textures (18 cells; 12%). The remaining 59 cells (40%) were similarly suppressed by both texture surrounds. Detailed analysis of texture modulation revealed two major components of surround effects: (1) fast nonspecific (“general”) suppression that occurred at about the same latency as excitatory responses and was found in all layers of striate cortex; and (2) differential response modulation that began about 60–70 ms after stimulus onset (about 15–20 ms after the onset of the excitatory response) and was less homogeneously distributed over cortical layers.

We have studied the postnatal development of presumptive axon terminals (puncta) which were recognized by antibodies to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and were located on the somata of area 17 neurons projecting to the ipsilateral area 18 of the visual cortex in cats ranging from 7 days of age to adulthood. Projection neurons were retrogradely labeled by injection of horseradish peroxidase conjugated to wheat germ agglutinin into the ipsilateral area 18. These neurons were mainly pyramidal in shape at all the developmental stages examined and the adult distribution of labeled cells was reached by 21 days. Subsequent GABA postembedding immunohistochemistry using high-resolution light microscopy was carried out to study the development of GABAergic terminals on cell bodies of identified projecting neurons in layers II–III. At all ages examined, we found perisomatic GABAergic puncta on these cells. Their density showed a significant increase from postnatal days 7 to 45, and then remained largely constant through adulthood. Since GABAergic puncta are considered the light-microscopic correlate of GABAergic synaptic terminals, our results support the idea of a developmentally regulated increase in the inhibitory activity of local interneurons on area 17 pyramidal neurons projecting to area 18 in the cat visual cortex which occurs within the same time frame as that of the acquisition of the mature operation of these cells.

The aim of the study was to determine whether memantine could slow down the changes seen in the rabbit and rat retina following ischemia/reperfusion. A “suction cup procedure,” which raises the intraocular pressure, was used to give an ischemic insult to the rabbit retina. The electroretinogram was recorded before ischemia and after 2 days of reperfusion. Memantine or saline (10 μl) was injected into the eye before ischemia. Immunohistochemistry was used to study the effect of ischemia/reperfusion on the GABA, ChAT, and αPKC immunoreactivities. Ischemia/reperfusion injury to the rat retina was induced by raising the intraocular pressure above the systolic blood pressure for 60 min, followed by reperfusion of 3–14 days. Memantine (5 mg/kg) or saline was injected i.p. at the onset of ischemia or reperfusion. Immunohistochemistry was used to study the effect of ischemia/reperfusion on the ChAT, αPKC, and Thy-1 immunoreactivities. In addition, morphometric analysis was carried out to determine the effects of ischemia/reperfusion on the thickness of the retina. Ischemia for 75 min caused a change in the nature of the normal GABA and ChAT immunoreactivities in the rabbit retina and a reduction in the b-wave of the electroretinogram. When memantine was injected into the vitreous humour at the onset of an ischemic insult, the changes in the GABA and ChAT immunoreactivities were reduced and the recovery of the reduced b-wave of the electroretinogram after 2 days reperfusion was enhanced significantly. Ischemia for 60 min followed by 3 days reperfusion showed a clear change in ChAT immunoreactivity in the rat retina. The Thy-1 immunoreactivity was only clearly altered after a reperfusion period of 7 days. Moreover, a measurable change in the thickness of the inner retinal layers was detected after 14 days of reperfusion. When given at the onset of ischemia, memantine counteracted the effect of ischemia/reperfusion to varying degrees. However, when memantine was given at the onset of the reperfusion this was not the case. The combined data show that a single injection of memantine given i.p. or intravitreally will protect the retina from a subsequent ischemic insult.

Results from earlier experiments indicate that different species of rodent vary both in the number of cone types found in their retinas and in the spectral sensitivities of the cone pigments. These features have now been examined in two types of hamster commonly used for research purposes: Syrian golden hamsters (Mesocricetus auratus) and Siberian dwarf hamsters (Phodopus sungorus). Electroretinogram (ERG) flicker photometry, behavioral discrimination tasks, and opsin antibody labeling were used to investigate hamster photoreceptors and their visual consequences. Results from the three approaches support the following conclusions: (1) The retinas of both species have an abundant population of rods containing a photopigment with peak sensitivity of about 498–500 nm; (2) Siberian dwarf hamsters have two classes of cone: one with maximum sensitivity in the ultraviolet (c. 360 nm), the other with peak sensitivity closely similar to that of its rod; and (3) Syrian golden hamsters have a class of cone with peak sensitivity at about 506 nm, but they lack a second cone type. Implications of these alternative arrangements are discussed.

The spatiotemporal structure of cortical activity evoked by diffuse light flashes was investigated in an isolated eyecup-brain preparation of the pond turtle, Pseudemys scripta. By combining a photomicroscopic image of the preparation with voltage-sensitive dye signals recorded by a 464-element photodiode array, the spread of depolarization within different cortical areas could be directly visualized with millisecond temporal resolution. Diffuse stimulation of the contralateral eyecup initially depolarized the visual cortex at the junction between its lateral and medial divisions in a small area rostral of the ventricular eminence. From this point, the depolarization spread at different velocities (10–100 μm/ms) depending upon the direction of travel. Since the initial depolarization was always in the rostral pole, the largest spread invariably occurred in a rostral → caudal direction. Within the confines of the medial visual cortex, depolarization spread at a constant velocity but slowed after entering the adjoining medial cortex. Increasing the stimulus illuminance increased the velocity of spread. Rostrocaudal spread of depolarization was also observed in response to electrical stimulation of the geniculocortical pathway and by direct focal stimulation of the cortical sheet. These data suggest that excitatory connections between pyramidal cell clusters play a prominent role in the initial activation of the cortex by diffuse retinal stimulation.

To gain insight into how vision guides eye movements, monkeys were trained to make a single saccade to a specified target stimulus during feature and conjunction search with stimuli discriminated by color and shape. Monkeys performed both tasks at levels well above chance. The latencies of saccades to the target in conjunction search exhibited shallow positive slopes as a function of set size, comparable to slopes of reaction time of humans during target present/absent judgments, but significantly different than the slopes in feature search. Properties of the selection process were revealed by the occasional saccades to distractors. During feature search, errant saccades were directed more often to a distractor near the target than to a distractor at any other location. In contrast, during conjunction search, saccades to distractors were guided more by similarity than proximity to the target; monkeys were significantly more likely to shift gaze to a distractor that had one of the target features than to a distractor that had none. Overall, color and shape information were used to similar degrees in the search for the conjunction target. However, in single sessions we observed an increased tendency of saccades to a distractor that had been the target in the previous experimental session. The establishment of this tendency across sessions at least a day apart and its persistence throughout a session distinguish this phenomenon from the short-term (<10 trials) perceptual priming observed in this and earlier studies using feature visual search. Our findings support the hypothesis that the target in at least some conjunction visual searches can be detected efficiently based on visual similarity, most likely through parallel processing of the individual features that define the stimuli. These observations guide the interpretation of neurophysiological data and constrain the development of computational models.

We studied the off-response of the rat ERG evoked with long duration, mesopic stimuli during light and dark adaptation, and after intravitreal injection of aspartate and (±)-cis-piperidine-2,3-dicarboxilic acid (PDA). At stimulus offset, the dark-adapted ERG always showed a rapid negative deflection followed by a positive deflection after which the potential returned to baseline. When the stimulus was turned off in the presence of a background of scotopic intensity, the positive deflection consisted of two components. One component was relatively small, fast, and insensitive to rod light adaptation. It resembled the d-wave of the rod ERG. The other component was slow and its amplitude grew with rod light adaptation. In the presence of aspartate, the fast-positive component was absent from the ERG while the remaining positive-going decay of the receptor potential had a time course similar to that of the slow-positive component in the untreated eye. Scotopically matched red and blue stimuli of mesopic intensity elicited equal ERG responses from the dark-adapted eye, including the two positive components in the off-response. These stimuli were also used to assess changes in the ERG off-response during recovery from a strong bleach. Even though the cone contribution to the rat ERG is very small, the presence of a small positive-going component in the off-response following an intense bleach suggested that this response originated from the cone pathway. PDA which suppresses the light response of hyperpolarizing bipolar cells and horizontal cells selectively eliminated the fast-positive component from the ERG. The findings of this study are inconsistent with the idea that the d-wave reflects the decay of the rod receptor potential. They support the possibility that signals from rods cross rod–cone gap junctions at mesopic light intensities, and drive second-order neurons in the cone pathway.

To determine the number of wide-field, monostratified ganglion cell classes present in the human retina, we analyzed a large sample of ganglion cells by intracellular staining in an in vitro, whole-mount preparation of the retina. Over 1000 cells were labeled by horseradish peroxidase or Neurobiotin; some 200 cells had wide dendritic trees narrowly or broadly stratified within either the inner (ON) or outer (OFF) portion of the inner plexiform layer. Based on dendritic-field size and the pattern and extent of dendritic branching, we have distinguished six wide-field cell groups. The giant very sparse ganglion cells included both inner and outer stratifying cells and were unique both for their extremely large dendritic field (mean diameter = 1077 μm) and extremely sparsely branched dendrites. Four of the cell groups had similarly large dendritic fields, ranging in mean diameter from 737 to 791 μm, but differed in the pattern and extent of dendritic branching, with the number of dendritic branch points ranging from a mean of 33 to 129. Of these four groups, the large very sparse group and the large dense group included both inner and outer stratifying cells, while the large sparse and large moderate groups consisted of inner stratifying cells only. The thorny monostratified ganglion cells were distinct from the other cells in having medium size dendritic fields (mean diameter = 517 μm) and moderately branched, inner stratifying dendritic trees with many thin, spiny, twig-like branchlets. All six groups had medium-size cell bodies, with mean soma diameters ranging from 17 to 21 μm. Though the physiological properties and central projections of human wide-field, monostratified ganglion cells are not known, some of the cells resemble macaque ganglion cells known to project to the lateral geniculate nucleus, the pretectum, or the superior colliculus.

Administration of a single subcutaneous dose of 5,7-dihydroxytryptamine (5,7-DHT) to newborn hamsters results in a significant increase in the density of serotoninergic (5-HT) fibers in the superficial layers of the superior colliculus (SC) and marked abnormalities in the uncrossed retinotectal projection when these animals reach adulthood (Rhoades et al., 1993). The present study was undertaken to determine whether elevation of 5-HT in the developing SC altered the visual representation in SC. Multi-unit recordings from SC cells demonstrated that the overall organization of the visual map in the superficial SC laminae was normal and that the receptive-field sizes for unit clusters were unchanged in the 5,7-DHT-treated animals. However, when a combination of CNQX and MK-801 was directly applied to the SC to block postsynaptic activity, the receptive fields of unit clusters (presumably retinotectal axon terminals) in the 5,7-DHT treated animals were significantly larger than those in the normally reared hamsters. These results are consistent with the conclusions that elevation of 5-HT levels in the developing SC reduces the postnatal refinement of the crossed retinotectal axons, and that mechanisms operating within the SC may act to maintain normal sizes for the receptive fields of its constituent neurons.

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate glutamatergic neurotransmission, and when pathologically overstimulated induce excitotoxic neuronal death. Of the two families of iGluRs, the non-NMDA receptors have received less experimental attention than the NMDA receptors as mediators of neuronal death in in vitro systems. We have demonstrated that non-NMDA receptor activation is highly lethal for neurons of the chick embryo retina, and further characterize this phenomenon here. Treatment of isolated retinas with any of the non-NMDA receptor agonists glutamate, AMPA, or KA, in the presence of the NMDA receptor antagonist MK-801, led to pathomorphology and cell death. KA was the most effective toxin. All of KA-induced toxicity could be blocked by selective AMPA receptor blockers. The toxicity of both AMPA and glutamate could be greatly increased using cyclothiazide, which blocks AMPA receptor desensitization. These results indicate that KA is the most powerful toxin because it is a non-desensitizing agonist at the AMPA receptors. Glutamate exhibited a paradoxical ability to prevent KA-induced toxicity as measured by a biochemical assay of cell death. Also, histological studies indicated that glutamate selectively blocked KA-induced pathomorphological changes in bipolar cells. This protective effect of glutamate was not mimicked by AMPA, NMDA, or any of several metabotropic receptor agonists, indicating that it may be mediated by a receptor of undescribed pharmacology.

Ascorbate, often used as an antioxidant in neural studies, may also serve as a neuromodulator in the vertebrate central nervous system (CNS), in that it modulates the synaptic actions of glutamate and dopamine. Retina of fish contain a high concentration of ascorbate. The release and/or uptake of neurotransmitters are related to membrane potential, which to a large extent is determined by the activity of K+ channels. As retinal bipolar cells are subject to synaptic input from glutamatergic and dopaminergic sources, the effects of ascorbate on voltage-dependent K+ currents (IK(V)) of the mixed rod–cone ON-center bipolar cells (Mb) in goldfish retinal slices were studied using whole-cell recording techniques. IK(V) was suppressed reversibly 60% by 100–200 μM ascorbate. The effect of ascorbate was not due to changes in pH, oxidative stress, lipid peroxidation, any Ca2+-dependent or Na+-dependent action. However, the suppressive effect of ascorbate was blocked by cholera toxin and Wiptide, a protein kinase A (PKA) inhibitor. It is concluded that ascorbate, at physiological concentrations, inhibits IK(V) of bipolar cells via a GS-protein-PKA system. This effect of ascorbate should be taken into account when using ascorbate as an antioxidant in retinal studies involving dopamine.

The high-affinity uptake of glutamate by glial cells and neurons of the central nervous system, including the retina, serves to inactivate synaptically released glutamate and maintains glutamate at low concentrations in the extracellular space. This uptake prevents accumulation of glutamate extracellularly and thus minimizes the possibility of glutamate neurotoxicity secondary to ischemic insult. One mechanism whereby glutamate neurotoxicity may occur in ischemic/hypoxic insult is through increased extracellular K+ reversing the electrogenic glutamate uptake into retinal glial (Müller) cells. We investigated glial uptake of the amino acids glutamate, GABA, and D-aspartate in the intact isolated rat retina under high extracellular K+ conditions and under conditions simulating ischemia. Immunocytochemical findings showed that uptake of glutamate and GABA by Müller cells in the intact isolated rat retina continues under conditions simulating ischemia and high extracellular K+ conditions, and uptake of D-aspartate also continues under high K+ conditions. However, under high K+ conditions, the glutamate uptake system saturates at a lower concentration of exogenous glutamate than in the normal K+ condition. These findings provide evidence that disruption of glutamate uptake by Müller cells is likely to be a significant contributing factor to excess glutamate accumulation in the extracellular space which can lead to neurotoxicity.

Recent work has indicated that cobalt, at sub-millimolar concentrations, blocks horizontal cell (HC) to cone feedback, without attenuating direct cone to second-order cell synaptic transmission. We utilized low concentrations (0.25–0.5 mM) of cobalt to test the contribution of the feedback circuit, and other possible cobalt-sensitive mechanisms, to the receptive-field surrounds of retinal neurons. In the great majority of cases, low cobalt blocked ganglion cell surrounds, and it invariably blocked driving the ganglion cell by extrinsic current injected into the HC network. Although low cobalt reduced the integrating area of the HC network, dopamine, which similarly constricted the HC receptive area, did not block ganglion cell surrounds. Low cobalt reduced a late depolarizing wave in the HC light-evoked waveform and selectively suppressed the depolarizing component of chromatic HCs, both signs of HC to cone feedback. Low cobalt also reduced or blocked completely the receptive-field surrounds of a small sample of bipolar and amacrine cells. These results implicate the HC to cone feedback synapse in the formation of the receptive-field surround of retinal neurons.

The distribution of AMPA-selective glutamate receptor subunits was studied in the cat retina using antisera against GluR1 and GluR2/3. Both antisera were localized in postsynaptic sites in the outer plexiform layer (OPL) as well as the inner plexiform layer (IPL). Immunoreactivity for GluR1 was seen in a subpopulation of OFF cone bipolar cells and a number of amacrine and ganglion cells. Within the IPL, processes staining for GluR1 received input from OFF and ON cone bipolar cells but not from rod bipolars. Labeling for GluR2/3 was seen in horizontal cells, an occasional cone bipolar cell, and numerous amacrine and ganglion cells. In the IPL, GluR2/3 staining was postsynaptic to cone bipolar cells in both sublaminae. AII amacrine cells which receive rod bipolar input were also labeled for GluR2/3. With both antisera, staining was limited to a single member of the bipolar dyad complex, providing morphological evidence for functional diversity in glutamatergic pathways.

GABAergic responses of acutely dissociated rat retinal neurons, including both bipolar cells (BCs) and other, morphologically round cells (RCs), were assayed with the fluorescent (FL), voltage-sensitive probe oxonol DiBaC4(5). Using intensified video microscopy and simultaneous recording, GABA responses were identified in one-third of cells in a typical microscope field; of these 85% hyperpolarized (0.05–0.3 log unit FL decreases) while the remainder depolarized (0.05–0.2 log unit FL increases). GABA-sensitive cells were also TACA-sensitive (trans-4-Aminocrotonic acid), and these ligands appeared interchangeable in ability to evoke responses. In RCs, an asymmetric co-responsive pattern was observed between GABA- and muscimol-evoked events. Muscimol-sensitive RCs responded well to GABA, but not all GABA-sensitive RCs responded to muscimol. In GABA-sensitive BCs, muscimol responses were typically weak or absent. Few BCs or RCs responded to CACA (cis-4-Aminocrotonic acid). Bicuculline-resistant GABA responses occurred in ∼80% of GABA-responsive RCs and BCs. Both bicuculline-sensitive (GABAA-like) and bicuculline-insensitive (GABAC-like) responses were resistant to picrotoxin. Although a small minority of GABA-sensitive cells hyperpolarized in response to R(+)baclofen, bicuculline-insensitive responses were not antagonized by 2-hydroxysaclofen, and were abolished in low [Cl−]o. Results suggested (1) that bicuculline-insensitive, Cl−-dependent, GABAC-like responses were broadly distributed and predominant among dissociated rat retinal neurons; (2) that muscimol was a particularly weak agonist for rat retinal BCs; and (3) that oxonol was a sensitive probe for retinal GABA responses.