Extracellular single-unit recordings were made from simple cells in area 17 of anesthetized cats. Cells were tested with drifting gratings under control and adapted conditions. Response amplitude and phase were measured as a function of either contrast or temporal frequency. Adapting not only reduces amplitude, but also retards phase. Adaptation alters the responses of simple cells in a particular way: the onset of the response to each cycle of a sinusoidally modulated stimulus is delayed. Once cells start to respond during each cycle, however, they generally recover to control levels, and the offset of the response is unaffected by adapting. The timing aftereffects are independent of the amplitude aftereffects. Timing aftereffects are tuned around the adapting temporal frequency, with a bias toward lower temporal frequencies. Adaptation thus modifies cortical responses even more specifically then previously thought. Firing rates are depressed primarily at response onset, even after several stimulus cycles have occurred following the end of adapting. Because all cells appear to adapt in this way, the data offer an opportunity to theorize about cortical connectivity. One implication is that inhibition onto a simple cell arises from other simple cells with similar response properties that fire a half-cycle out of phase with the target cell.

The responses of inferior temporal (IT) neurons may depend on the behavioral context of the stimuli; e.g. in Konorski tasks responses to two successively presented physically identical stimuli can be markedly different. This effect has been interpreted as being linked to the behavioral task, and to be involved in short-term memory and/or the temporal comparison of successively presented stimuli. We tested whether this behavioral context effect also occurs when the monkey is not executing a Konorski task, i.e. no temporal comparison of stimuli is being performed. Responses of the same IT neurons under two behavioral conditions were compared using the same temporal stimulus sequence (but different stimuli): a Konorski task and a Fixation task. We found that the occurrence of the behavioral context effect did not depend on the execution of the short-term memory task. The observed decline in the level of responses to repeated presentation of similar stimuli is interpreted as being a passive mechanism involved in recency detection, which occurs even if the recency information is not useful for the task. The importance of these results in the interpretation of “task-related” neuronal responses is discussed.

The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4/5 are important in a variety of developmental processes in the peripheral and central nervous systems. These molecules bind to a low-affinity receptor and to distinct high-affinity receptors. The high-affinity receptor for NGF is the proto-oncogene product, p140trkA(trkA). Isoforms of p140trkA, p145trkB(trkB), and p140trkC(trkC), are the primary high-affinity receptors for BDNF and NT-3, respectively. We evaluated the developmental regulation of the high-affinity neurotrophin receptors in the rat retina using polyclonal antibodies directed to a highly conserved region of the C-terminus of the p140trkA isoforms (pantrk) and antibodies directed to unique amino-acid sequences of p140trkA, p145trkB, and p140trkC. Immunoreactivities for trkA and trkB, as well as pantrk, were detected in the developing retina and showed similar distributions. At similar antibody concentrations, trkC immunoreactivity was not detected. In the embryo, immunoreactivities were present in cells located throughout the neuroblastic retina, especially in the inner retinal layers, and in fibers in the nerve fiber layer and optic nerve. In the newborn retina, immunoreactivities for these two receptor isoforms were localized to numerous somata in the inner nuclear layer (INL), as well as to cells in the ganglion cell layer (GCL) and axons in the nerve fiber layer and optic nerve. A similar pattern of immunostaining persisted throughout the first postnatal week. By postnatal day-10, immunostaining was confined to large-diameter cells in the GCL, both heavily stained and lightly stained cells in the INL and a plexus of processes in the inner plexiform layer (IPL). In the adult retina, specific immunoreactivity was present in sparsely distributed, lightly and moderately stained, large cells in the GCL, numerous lightly and moderately stained cells throughout the INL and in plexuses of processes in the IPL and outer plexiform layer. Specific immunostaining of photoreceptor cells was not observed. These observations indicate that high-affinity receptors for the neurotrophins are expressed in cells of the inner retina, including ganglion cells, during the period of retinal development. This is congruent with roles for neurotrophins in such processes as survival, differentiation and synapse formation of cells in the developing visual system.

Dark-adapted adults' electroretinographic b−wave thresholds are —2 log units below a−wave thresholds and ~3 log units above the perceptual threshold, and their perceptual and the visually evoked cortical potential (VEP) thresholds are similar. Dark-adapted infants' scotopic a− and b−wave thresholds for full-field stimuli are both about 0.5 log units above those of adults, but their scotopic VEP thresholds for such stimuli have not been studied. We obtained scotopic VEP thresholds for brief, full-field stimuli from dark-adapted, infants and adults to consider the relationships of the cortical responses to the responses of more distal structures, namely the rod photoreceptors (scotopic a−wave) and ON-bipolars (scotopic b−wave). The median VEP threshold of infants is 0.5 log unit above that of adults. Thus, the relationships of a− and b−wave and VEP thresholds in infants are similar to those in adults. These results are consistent with rod cell immaturities being the primary determinant of the difference between infants' and adults' thresholds.

Responses to full-field colored flashes (red, blue, and green) were compared with those to illuminancematched white flashes in area V1, optic radiations, and the lateral geniculate nucleus of two alert macaques. Laminar profiles of visual evoked potentials (VEPs), current source density, and multiunit activity were obtained using multicontact electrodes capable of sampling from all layers of cortex or lateral geniculate nucleus, simultaneously. In striate cortex, stimulation with colored flash enhanced transmembrane current flow dramatically in both layer 4c and the supragranular laminae. Stimulation with red evoked the largest enhancement in every electrode penetration. The mean peak amplitudes of current sinks evoked by red were 203% and 537% of those evoked by white light in layer 4c and the supragranular laminae, respectively. Color effects in VI were preceded by an initial epoch of wavelength-insensitive activity. In layer 4c, the red effect reached significance, on average, at 47 ms, or ≈24 ms after the onset of transmembrane current flow. In the supragranular layers, the red effect reached significance, on average, at 55 ms, or ≈14 ms after the onset of current flow. Recordings from optic radiations in the white matter below V1 and from lateral geniculate nucleus showed no significant difference in the responses to color and illuminance-matched white light. Enhancement of supragranular current flow with color stimulation increased the contribution of these laminae to the generation of the surface VHP. Comparison of the surface VHP wave forms evoked by white and color stimuli may, therefore, help to differentiate the responses of the granular and supragranular laminae.

Previous work using homogenate binding has shown that the development of (+)-5-methyl-10, ll-dihydro-5H-dibenzo[a, d]-cyclohepten-5, 10imine maleate (MK-801) binding in cat visual cortex increases from 21 days to 42 days, the height of the plastic period, and decreases in adulthood. We have studied the generality of this finding by examining the development of NMDA binding sites in several brain regions and by examining the development of other binding sites in the visual cortex. After confirming the original finding, we extended it by showing that the sensitivity of MK-801 binding sites to glutamate and glycine decreases when the cat becomes an adult. We then examined the regional specificity of MK-801 binding. Retinal binding did not change significantly with age. Binding in both visual cortex and hippocampus increased significantly from 7 days to 42 days regardless of whether binding was measured per milligram wet weight or per milligram protein. The decline from 42 days to adulthood was less dramatic in the hippocampus than in the visual cortex and was statistically significant only when binding was measured per milligram protein. Saturation analyses also showed a difference in the two structures. Bmax in the visual cortex, but not in the hippocampus, decreased from 42 days to adulthood. To determine whether these developmental changes were specific to MK-801 binding sites, we compared the age-dependent binding of MK-801, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazoIepropionic acid (AMPA), and muscimol. Like MK-801, kainate binding increased from 7 days to 42 days and decreased from 42 days to adulthood. AMPA and muscimol binding showed a similar increase in binding from 7 days to 42 days but did not decrease significantly from 42 days to adulthood. Displacement experiments suggest that AMPA and kainate bind to separate sites. The 42-day peak in NMDA and kainate binding suggests that their associated receptors may have a role in determining the plastic period of visual cortex.

The optic nerve in two species of subterranean mole-rats (Spalacidae) has been examined at the ultrastructural level. The axial length of the eye and the diameter of the optic nerve are 1.9 mm and 52.5 μm in Spalax leucodon, and 0.7 mm and 80.8 μm in Spalax ehrenbergi, respectively. An anti-glial fibrillary acidic protein postembedding procedure was used to distinguish glial cell processes from axons. In both species, the optic nerve is composed exclusively of unmyelinated axons and a spatial distribution gradient according to the size or the density of fibers is lacking. The optic nerve of S. leucodon contains 1790 fibers ranging in diameter from 0.07–2.30 μm (mean = 0.57 μm), whereas in S. ehrenbergi, only 928 fibers, with diameters of 0.04–1.77 μm (mean = 0.53 μm) are observed. In S. ehrenbergi, a higher proportion of glial tissue is present and the fascicular organization of optic fibers is less obvious. Distribution gradients according to size frequency or density of fibers in the optic nerve are absent in both species. Comparison with other mammals suggests that although ocular regression in microphthalmic species is correlated with a significant decrease in the total number of optic fibers and the relative proportion of myelinated fibers, no difference in the absolute size range of unmyelinated axons is observed. The total absence of myelinated fibers in Spalax may be related to the subcutaneous location of the eyes. The unique presence of unmyelinated fibers in the optic nerve is discussed in relation to the possible conservation of a single class of W-like ganglion cells in the retina, in relation to photoperiodic perception.

An enzyme of bovine retina that catalyzes oxidation of retinaldehyde to retinoic acid was purified to homogeneity and a monoclonal antibody (mAb H-4) was generated. MAb H-4 recognized a single component (Mr = 55,000) in extracts of bovine retina and other bovine tissues. The antibody showed no cross-reactivity with extracts of rat, monkey, or human retinas. A 2067 bp cDNA was selected from a retina cDNA expression library using mAb H-4. The cDNA hybridized with a similarly sized, moderately abundant mRNA prepared from bovine retina. Nucleotide sequence analysis indicated that the cDNA contained a single open reading frame encoding 501 amino acids that have 88% sequence identity with the amino-acid sequence of human hepatic Class 1 aldehyde dehydrogenase. Amino-acid sequence analysis of purified enzyme demonstrated that the cDNA encodes the isolated enzyme. MAb H-4 specifically labeled the somata and processes of a subset of amacrine cells in bovine retinal sections. Labeled amacrine somata were located on both sides of the inner plexiform layer, and their processes ramified into two laminae within the inner plexiform layer. The inner radial processes of Müller (glial) cells were weakly reactive with mAb H-4. Weak immunostaining of amacrine cells was found in monkey retina with mAb H-4, but no signal was detected in rat or human retina. The results provide further evidence for metabolism and function of retinoids within cells of the inner retina and define a novel class of retinal amacrine cells.

We have studied the glial investment of ganglion cells of the cat's retina, orienting the sections taken for electron microscopy so that the investment could be traced from the soma along the axon. The soma of each ganglion cell is covered by a close-fitting, continuous sheath formed by Müller cells. The axon hillock and the first part of the initial segment are invested by an extension of the somal sheath, and are thus enclosed in the same glial compartment as the soma. The initial segment extends a few microns past the Müller cell sheath; this last length of the initial segment is contacted by numerous processes of astrocytes, which converge on it in a pattern found also on nodes of the same axons, in the optic nerve. Beyond the initial segment, the intraretinal lengths of the axons are invested by both Müller cells and astrocytes, but the investment is strikingly incomplete. Large areas of axonal membrane have no glial cover, and lie close to other axonal membranes. The sequential arrangement of these distinct forms of glial wrapping of the soma, initial segment, and axon is described here for the first time. It is suggested that this pattern of glial investment controls the flow of current between dendrite and initial segment of the ganglion cell, defines the site of initiation of action spikes, and controls the formation of synapses on the soma and initial segment.

Pupillary area was measured in urethane-anesthetized cats as a function of retinal illuminance. When appropriate corrections are made for differences in experimental procedures, it was found that the pupillary response of the urethane-anesthetized cat's eyes to light was basically unchanged from that of the alert behaving cat. This preparation may therefore be a very satisfactory one in which to study the pupillary response pathway in a higher mammal.

The goal of this work was to provide a detailed quantitative description of the recepii ve-field properties of one of the types of rarely encountered retinal ganglion cells of cat; the cell named the Q-cell by Enroth-Cugell et al. (1983). Quantitative comparisons are made between the discharge statistics and between the spatial receptive properties of Q-cells and the most common of cat retinal ganglion cells, the X-cells. The center-surround receptive field of the Q-cell is modeled here quantitatively and the typical Q-cell is described. The temporal properties of the Q-cell receptive field were also investigated and the dynamics of the center mechanism of the Q-cell modeled quantitatively. In addition, the response vs. contrast relationship for a Q-cell at optimal spatial and temporal frequencies is shown, and Q-cells are also demonstrated to have nonlinear spatial summation somewhat like that exhibited by Y-cells, although much higher contrasts are required to reveal this nonlinear behavior. Finally, the relationship between Q-cells and Barlow and Levick's (1969) luminance units was investigated and it was found that most Q-cells could not be luminance units.

Calbindin D-28K is a calcium-binding protein found in the cone but not rod photoreceptor cells in the retinas of a variety of species. Recent studies of the monkey retina indicated that calbindin D-28K may be expressed preferentially in non-foveal regions of the retina. In the current studies of human retinas, immunohistochemical experiments demonstrated that calbindin D-28K is reduced or absent in the fovea and parafovea, but prevalent in the perifovea and periphery. These findings were supported by the quantification of calbindin D-28K in 1-mm trephine punches obtained from different regions of the human retina. The specificity of the anti-calbindin D-28K antibodies used in these studies was confirmed by Western blot analysis using purified calbindin D-28K. The protein was purified from retinal tissue and its identity confirmed by partial amino-acid sequence analysis. The expression of calbindin D-28K did not correlate with the spectral properties of the cones, rather to their position in the retina. The study of spatially expressed genes, like the one encoding calbindin D-28K, may help explain the patterns of retinal degeneration seen in some human cone-rod dystrophies.

The receptive fields of cells in the primary visual cortex (area 17 or V1) show clear orientation selectivity, unlike those of the lateral geniculate nucleus (LGN) cells which provide their visual input. The intrinsic circuitry of V1 cells is believed to be partly responsible for this selectivity. We investigated the influence of ascending projections from neurons in the lower layers (5 and 6) of V1 on the orientation selectivity of single neurons in the upper layers (2, 3, and 4) by reversibly inactivating (“blocking”) lower layer neural activity with iontophoretic application of γ-aminobutyric acid (GABA) while recording from upper layer cells in the prosimian primate, Galago crassicaudatus. During lower layer blocking, the majority (20/28 = 71.4%) of upper layer neurons exhibited a change in the orientation of their preferred stimulus, a reduction in their orientation tuning, and/or an increase in their response amplitude. Twelve (42.9%) neurons exhibited shifts in their preferred orientation averaging 11 (±4) deg. These neurons were located, on average, 272 (±120) μm tangential from the vertical axis of the pipette center. Eleven neurons (39.2%) exhibited an average reduced orientation tuning of 52.5%. Their average location was 230 ± (115) ftm away from the vertical axis of the pipette. Five (17.9%) neurons with average location 145 (±75) firn from the vertical axis exhibited both effects. Two (7.1%) neurons that exhibited significant increases in response amplitude to stimulus angles within 10 deg of the peak excitatory stimulus without changes in orientation selectivity or tuning were located less than 100 μm from the vertical axis. The effects on the orientation tuning of cells were restricted in all cases to within ±30 deg of the preferred stimulus orientation. This suggests that layer blocking affects cells with preferred stimulus orientations similar to those of the recorded neurons. Only cells located within 500 μm tangential to the vertical axis of the injection site exhibited these effects. These results suggest that cells within layers 5 and 6 provide organized, orientation-tuned inhibition that sharpens the orientation tuning of cells in the upper cortical layers within the same, or closely neighboring, cell columns.

We have previously reported that the responses of individual neurons in macaque visual area MT elicited by movement of contrast-reversing heterochromatic red/green borders are largest when the two hues are “balanced” or isoluminant (Dobkins & Albright, 1994). This “neural” isoluminant point was found to vary somewhat across the sample of neurons. Here, we compare the average neural isoluminant point in area MT to a behavioral measure of isoluminance, obtained using a modification of an oculomotor procedure developed by Chaudhuri and Albright (1992). These behavioral estimates of isoluminance closely parallel the neuronal data obtained from area MT. In accordance with previous evidence (e.g. Lee et al., 1988; Kaiser et al., 1990; Valberg et al., 1992), this correlation suggests that activity within the dorsal/magnocellular stream underlies behavioral expression of chromatic isoluminance.

Microelectrodes were used to record from red and green cones of the turtle Pseudemys scripta elegans. The purpose of this study was to determine the action spectra of the red and green cone photopigments, and to look closely for direct interactions between the two cone classes. An isolated retina preparation was employed so that cones could be stimulated from the outer segment side, thereby avoiding the oil droplets that reside in the inner segments of many cones and normally filter incident light. In agreement with some previous electrophysiological studies, we found little evidence for significant direct connections between red and green cones. Exceptions to this rule are noted and discussed. Measurements indicate that this result does not appear to be due to a general loss of cone connectivity in the isolated retina preparation. Action spectra of the cone photopigments differed markedly from action spectra reported for cones in the eyecup preparation. In contrast to cones in the eyecup, cones in the isolated retina showed higher short-wavelength sensitivity and had action spectra that were adequately described by photopigment nomograms. A model of cone optical properties suggests that in the eyecup up to about 40% of the light that reaches a cone outer segment may do so without first passing through an oil droplet.

Direction-selective (DS) ganglion cells of the mammalian retina have their dendrites in the inner plexiform layer (IPL) confined to two narrow strata. The same strata are also occupied by the dendrites of cholinergic amacrine cells which are probably presynaptic to the DS ganglion cells. GABA is known to play a crucial role in creating DS responses. We examined the types of GABAA receptors expressed by the cholinergic amacrine cells and also those expressed by their presynaptic and postsynaptic neurons, by applying immunocytochemical markers to vertical sections of rat retinas. Double-labelling experiments with antibodies against choline acetyltransferase (ChAT) and specific antibodies against different GABAA receptor subunits were performed. Cholinergic amacrine cells seem to express an unusual combination of GABAA receptor subunits consisting of α2-, β1-, β2/3-, γ2-, and δ-subunits. Bipolar cells, which could provide synaptic input to the DS circuitry, were stained with antibodies against the glutamate transporter GLT-1. The axon terminals of these bipolar cells are narrowly stratified in close proximity to the dendritic plexus of displaced cholinergic amacrine cells. The retinal distribution of synaptoporin, a synaptic vesicle associated protein, was studied. Strong reduction of immunolabelling was observed in the two cholinergic strata. The anatomical findings are discussed in the context of models of the DS circuitry of the mammalian retina.

Using light-microscopic immunocytochemistry against tyrosine hydroxylase, we have investigated the morphology of dopaminergic cells in 23 species of fishes representing various systematic classes and subclasses and which live in very different habitats. We have, for the first time, observed teleosts with dopaminergic amacrine cells. Thus, in both bony and cartilaginous fishes, dopaminergic cells are differentiated as interplexiform and amacrine cells. The differentiation of dopaminergic cells into amacrine or interplexiform cells in fishes correlates with the absence or presence of cones. In pure-rod retinae, they occur as amacrine cells, and in mixed rod/cone retinae, they occur as interplexiform cells. We conclude therefore that the differentiation of retinal dopaminergic cells in fish does not depend on the evolutionary or systematic classification of a given species. Rather, it is correlated with the occurrence of rods and/or cones, and thus linked more closely to the habitat. We argue that, in fish, the presence of cones and cone-specific horizontal cells may be responsible for inducing dopaminergic cells to differentiate as interplexiform cells. Possible functions of dopamine in all-rod retinae, which may not require adaptation, may include neuromodulation in the inner plexiform layer for the sensitization of the rod pathway, the shaping of biological rhythms, and the control of eye growth.

Latencies to small flashing spots of light were measured in different layers of areas V1 and V2 in anesthetized and paralyzed macaque monkeys. The shortest latencies were found in layers 4Cα and 4B of area V1. Latencies in layer 4Cβ were on average 20 ms longer than those in 4Cα and 4B. The shortest latencies in area V2 were observed in the infragranular layers and they did not differ significantly from those found in the infragranular layers in V1. Similarly, latencies in the supragranular layers of V2 were not significantly different from those measured in the supragranular layers of V1. These results show that, in area V1, neurons of the magnocellular pathway are activated on average 20 ms earlier than those of the parvocellular pathway. Our data also suggest that much processing begins simultaneously in areas V1 and V2.

Objects falling across the physiological blind spot appear “complete” despite the absence of photoreceptors. Completion of objects may occur across the blind spot because (1) the blind spot is filled in with the background (the associative explanation); (2) the opposite sides of the blind spot may be contiguously represented in the cortex (i.e. the blind spot is simply sewn up —the retinotopic explanation); or (3) the blind spot may be sewn up, with compensatory expansion occurring around the blind spot (the compensation explanation). These theories would predict no size distortions regardless of object size; constant size distortions regardless of object size; and distortions that depend on the size of the object, respectively. To evaluate these explanations, we measured size distortions at the blind spot. We measured length distortions at the blind spot using a criterion-free two-alternative forced-choice method with feedback. Observers compared the lengths of test bars presented across the blind spot with lengths of reference bars presented at the corresponding location in the fellow eye. Test bar lengths ranged from 7–14 deg. Reference bar lengths were in the range of ±3 deg of test bar length. From the observers' responses the perceived length of each bar at the blind spot was estimated. Estimates of the precision of length discrimination at the blind spot were also obtained. Our results were consistent with the associative explanation. In all seven observers, length distortions at the blind spot were smaller than 1 deg (<20% of the vertical height of the blind spot) for all bar lengths tested. For bars that were presented across the blind spot, the precision with which observers could discriminate length was comparable to that of normal periphery (Weber fraction ≈20%). Both the veridicality and precision of perceived length are preserved around the blind spot.