Using rhodamine-labelled latex beads as a retrograde tracer, we have shown that a subset of the neurons projecting from the lateral thalamic nucleus to the optic tectum of the leopard frog are neuropeptide Y-like immunoreactive (NPY-IR). In juvenile frogs, approximately twice as many lateral thalamic nucleus cells from this area project to the ipsilateral tectum as project to the contralateral tectum. NPY-IR cells make up 25% of the projection to the ipsilateral tectum and 13% of the projection to the contralateral tectum. The ipsilateral NPY-IR projection from the lateral nucleus was present in tadpoles and was similar in its characteristics to that found in the juvenile frog. However, the contralateral tectal projection was virtually nonexistent in these animals. The results of these experiments suggest that NPY from the lateral nucleus is released into the ipsilateral tectal neuropil in both the developing and adult frog.

The synaptic connections of amacrine cells synthesizing or accumulating serotonin in the retina of the cane toad, Bufo marinus, were studied by using preembedding double-labeling electron-microscopic immunocytochemistry. The binding sites of an anti-serotonin antibody were revealed by the diaminobenzidine reaction, whilst a colloidal gold-conjugated secondary antibody was used to detect an antibody to phenylalanine hydroxylase. Since the latter antibody recognizes tryptophan 5-hydroxylase, one of the synthesizing enzymes for serotonin, as well as tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis, the double labeling of the present study enabled us to identify three groups of labeled profiles at the ultrastructural level. The profiles of serotonin-synthesizing amacrine cells contained both diaminobenzidine reaction product and colloidal gold particles, whilst those of serotonin-accumulating and dopaminergic amacrine cells contained only diaminobenzidine reaction product or colloidal gold particles, respectively. The synapses of serotonin-synthesizing or serotonin-accumulating amacrine cells were distributed all through the inner plexiform layer of the retina. The profiles of serotonin-synthesizing amacrine cells predominantly received synapses from, and made synapses onto, unlabeled amacrine cell dendrites. They also received synapses from, and made synapses onto, bipolar cell terminals. They also made synapses onto presumed ganglion cell dendrites. However, the profiles of serotonin-accumulating cells made synapses only with unlabeled amacrine cell processes. There were close contacts between the profiles of serotonin-synthesizing and serotonin-accumulating amacrine cells. No synaptic relationships were observed between dopaminergic and serotonin-synthesizing or serotonin-accumulating amacrine cells. These observations indicate that serotonin-synthesizing amacrine cells and serotonin-accumulating amacrine cells in the retina of Bufo marinus are involved in different microcircuits in visual information processing.

The modulatory influence of pretectal neurons on retino-geniculate transmission in the cat was studied by cross-correlation analysis of single-unit activity simultaneously recorded from the dorsal lateral geniculate nucleus (dLGN) and the pretectum (PT) and with reversible inactivation of the PT by GABA microiontophoresis during simultaneous visual stimulation of PT and dLGN neurons. Visually induced population activity in PT nuclei was achieved by a moving (or counterphasing) grating which was presented in the background of the light spot used to stimulate the dLGN neuron. As a control, the light spot was presented on a stationary grating to avoid stimulation of PT neurons but to yield the same illumination of the background. Extracellularly recorded dLGN relay cells of the X- and Y-type were found to be differentially affected by the PT-dLGN projection. During visual stimulation of PT cells, X cells were strongly inhibited and this effect was significantly reduced during PT inactivation. By contrast, the visual responses of most Y cells were affected neither by PT stimulation nor by PT inactivation. In addition, the temporal structure of spike patterns during the light response was examined with autocorrelograms and spike-interval distributions. X-on cells often exhibited a multimodal interval distribution and oscillatory type of activity. During stimulation of the PT interval distributions changed in a characteristic manner and oscillations disappeared. Both effects could be almost totally cancelled by PT inactivation. By contrast, the temporal structure of Y-cell responses was not affected. Our results demonstrate for the first time a pretectal modulation of retino-geniculate transmission in cat dLGN which is clearly different for X and Y cells. This influence seems to be mediated via (inhibitory) interneurons, since we found no indication for a direct coupling between PT and dLGN units. This projection might contribute to the well-known phenomenon of saccadic suppression.

It is now well established that environmental signals mediated via neurotransmitters and hormones can induce responses in cells which involve a cascade of receptors, G proteins, and second messengers. These in turn can induce transcription factors which regulate long-term changes in gene expression. It has been proposed that the stimulus-transcription coupling properties of these DNA-binding proteins can be exploited to visualize activated neurons by way of immunostaining. We have used standard immunohistochemical techniques to detect the expression of one specific transcription factor, Zif268, in the visual cortex (area 17, V1) of vervet monkeys (Cercopithecus aethiops). Immunopositive neurons were present in large numbers throughout the visual cortex of the normal animal, being concentrated in layers 2/3 and 6 and at moderate levels in 4Cβ and 5. To determine if Zif268 expression was affected by visual stimulation in the monkey, we restricted light input to one eye with the aim of revealing ocular-dominance columns in striate cortex. We found that short-term monocular deprivation induced either by enucleation, intravitreal TTX injection, or eyelid suturing resulted in dramatic changes in Zif268 levels, revealing vertically oriented columns of reduced Zif268 staining interdigitated with columns of normal expression. Furthermore, these columns were discernible after just 2 h of monocular blockade. A comparison of the ocular-dominance pattern obtained with Zif268 immunostaining and cytochrome oxidase histochemistry in long-term monocularly deprived animals showed a coincident reduction of both markers along columns that were precisely aligned in adjacent sections, indicating that Zif268 expression is restricted to cortical regions of high metabolic activity. Simultaneous immunostaining for Zif268 and the calcium-binding proteins calbindin and parvalbumin showed a negative correlation, suggesting that the Zif268 protein may be expressed selectively within excitatory neurons. A similar approach with immunostaining for neurofilament and microtubule-associated proteins (SMI-32 and MAP2) revealed pyramidal neurons which were regularly found to contain a Zif268-positive nucleus. Furthermore, confocal images of lucifer yellow filled neurons possessing Zif268-positive nuclei all showed pyramidal morphology. Taken together, these results point to activity-dependent expression of Zif268 within a subset of excitatory neurons.

Recent electrophysiological and anatomical experiments in rats and cats have shown that treatment with the neurotrophic factor — nerve growth factor (NGF) — prevents the effects of monocular deprivation (MD) at the level of visual cortex and lateral geniculate nucleus. We tested whether NGF treatment was effective in preventing MD effects on visual behavior of monocularly deprived kittens. Behavioral visual acuity was measured in kittens that had been monocularly deprived and treated intraventricularly with NGF for 2 weeks during the critical postnatal period. The detrimental effects of MD on behavioral visual acuity were found to be largely prevented by NGF treatment.

The intergeniculate leaflet (IGL) is an integral part of the circadian visual system. It receives direct retinal input and relays photic information to the circadian clock in the suprachiasmatic nucleus (SCN) through a geniculohypothalamic tract (GHT). In both rat and hamster, neuropeptide Y immunoreactive (NPY-IR) IGL cells project through the GHT to the SCN. However, the hamster GHT also contains enkephalin-IR (ENK-IR) fibers, presumably of IGL origin. In the present investigations, the IGL was examined for NPY-, ENK-, or dual-IR cells. Their projections to the SCN, contralateral IGL and pretectum were also studied. The results show that the hamster IGL contains both NPY- and ENK-IR neurons and that about 50% of these are immunoreactive to both peptides. Double-label retrograde analysis indicates that cells of each peptide class project to the SCN. Similarly, IGL neurons, many of which are NPY- and ENK-IR, project to the pretectum, particularly the posterior limitans nucleus. While numerous IGL neurons project contralaterally, very few are NPY- or ENK-IR.The distribution of SCN- and pretectum-projecting cells, in conjunction with the distribution of peptide-IR neurons, allows expansion of the IGL definition to include the region medial to the ventral lateral geniculate nucleus (VLG). The VLG is ventrolateral to the IGL and does not contain either neurons projecting to the SCN nor NPY- or ENK-IR cells, but does have numerous neurons projecting to the pretectum. The results substantiate and expand the previous definition of the hamster IGL, elaborate the species difference in IGL organization, and demonstrate the increased breadth of the circadian visual system.

Examination of the Limulus median optic nerve with low-magnification light microscopy allows clear visualization of an ultraviolet-sensitive mini-ommatidium enshrouded by pigment cells, glial cells, and guanophores. Serial 1-μm sections of median optic nerves containing mini-ommatidia revealed the presence of a single, heavily pigmented photoreceptor (retinular) cell and a single, unpigmented arhabdomeric cell. Computer-assisted serial reconstructions from 1-μm sections confirmed the presence of two cells, each bearing a nucleus, and two axons leaving the mini-ommatidium. The retinular cell is morphologically similar to retinular cells from the median and lateral eyes. Its rhabdomere appears to be a continuous sheet of microvilli with much infolding. The structure of the arhabdomeric cell is nearly identical to those found in the median ocellus. As in other photoreceptors in Limulus, the retinular cell of the mini-ommatidium is innervated by efferent fibers from the brain. Each mini-ommatidium generates a single train of nerve impulses in response to light, presumably from the arhabdomeric cell. Measurement of the spectral sensitivity of the mini-ommatidium based upon a constant-response criterion indicated that the retinular cell is maximally sensitive to near ultraviolet light with λmax = 380 nm. Comparison of intensity-response functions revealed that those of the mini-ommatidium are significantly steeper than those of the ocellus almost certainly as the result of neural processing in the ocellus which is absent in the mini-ommatidium.

Many psychophysical studies of various visual tasks show that performance is generally better for binocular than for monocular observation. To investigate the physiological basis of this binocular advantage, we have recorded, under monocular and binocular stimulation, contrast response functions for single cells in the striate cortex of anesthetized and paralyzed cats. We applied receiver operating characteristic analysis to our data to obtain monocular and binocular neurometric functions for each cell. A contrast threshold and a slope were extracted from each neurometric function and were compared for monocular and binocular stimulation. We found that contrast thresholds and slopes varied from cell to cell but, in general, binocular contrast thresholds were lower, and binocular slopes were steeper, than their monocular counterparts. The binocular advantage ratio, the ratio of monocular to binocular thresholds for individual cells, was, on average, slightly higher than the typical ratios reported in human psychophysics. No single rule appeared to account for the various degrees of binocular summation seen in individual cells. We also found that the proportion of cells likely to contribute to contrast detection increased with stimulus contrast. Less contrast was required under binocular than under monocular stimulation to obtain the same proportion of cells that contribute to contrast detection. Based on these results, we suggest that behavioral contrast detection is carried out by a small proportion of cells that are relatively sensitive to near-threshold contrasts. Contrast sensitivity functions (CSFs) for the cell population, estimated from this hypothesis, agree well with behavioral data in both the shape of the CSF and the ratio of binocular to monocular sensitivities. We conclude that binocular summation in behavioral contrast detection may be attributed to the binocular superiority in contrast sensitivity of a small proportion of cells which are responsible for threshold contrast detection.

Previous studies on fish retina have suggested that a curved, non-fused embryonic fissure is associated with, and perhaps caused by, asymmetric growth along the retina's marginal germinal zone (where neurons and Miiller glia are added appositionally throughout life). In this report retinal growth was measured directly in adult green sunfish (Lepomis cyanellus), which has a curved, non-fused embryonic fissure. Growth was asymmetric in both small and large fish: ventral and nasal retina grew more than temporal and dorsal retina. This asymmetry was due to different net rates of cellular addition, rather than differential passive expansion. The absolute rates of retinal growth in the centroperipheral direction were roughly exponential functions of fish size—smaller fish grow faster than large fish—but the area of new retina added per unit time did not vary with fish size. Visual implications of asymmetric retinal growth are evaluated.

This study investigates the receptive-field structure of mechanisms operating in human color vision, by recording visual evoked potentials (VEPs) to multiharmonic gratings modulated either in luminance or color (red-green). Varying the Fourier phase of the harmonics from 0 deg to 90 deg produced a family of stimulus profiles that varied from lines to edges. The stimuli were contrast reversed to elicit steady-state VEPS, and also randomly jittered (at a higher temporal frequency than the contrast reversal) to ensure that the evoked response resulted from the polarity reversal, rather than from local variation of luminance or color. Reliable VEPs were recorded from both luminance and chromatic stimuli at all phases, suggesting that the mechanisms sensitive to chromatic contrast and those sensitive to luminance contrast have both symmetric and asymmetric receptive fields. Contrast thresholds estimated by extrapolation of the contrast response curves were very similar to psychophysical thresholds for phase discrimination, suggesting that the VEP response is generated by mechanisms mediating phase discrimination. The results support the idea that human color mechanisms have receptive fields with a variety of spatial symmetries (including odd- and even-symmetric fields) and that these mechanisms may contribute to phase discrimination of chromatic stimuli in a similar way to what has been suggested for luminance vision.

The spatio-temporal receptive-field structure of 54 phasic W cells in cat retinas has been examined using the reverse-correlation method of Jones and Palmer (1987). Within this sample, 12 cells had on-center, 16 off-center, and 26 on-off receptive fields. Three of the on-center and seven of the on-off cells were directionally selective. Forty percent of the cells in this sample had local receptive fields consisting of two or more distinct subregions. However, no correlation was observed between the number of subregions in the local receptive field and other response properties such as center sign or direction selectivity. In all cases, individual subregions, including those in on-off cells, appear to be produced by a half-wave rectification of the input signal. For 76% of the cells, these local receptive fields were contained within large suppressive fields which could be seen to extend for at least 10 deg in all directions with no apparent spatial structure. The mechanism producing the suppressive field also appears to involve a rectification of the input signal, and has a relatively high spatial resolution. Furthermore, the suppressive field itself is only responsive to moving or flickering stimuli; large, stationary gratings have no effect on the output of the local receptive-field mechanism. Thus, the overall receptive-field organization of these cells is particularly well suited for detecting local motion. The remaining 24% of cells in the sample lacked suppressive fields, and consequently responded well to large moving stimuli, but these cells were otherwise similar in their receptive-field properties to cells with suppressive fields. The significance of these properties is discussed in the context of the projections of phasic W cells to the superior colliculus and accessory optic system.

There is controversy in the literature concerning whether or not neurons in the cat's posteromedial lateral suprasylvian (PMLS) visual cortex are orientation selective. Previous studies that have tested cells with simple bar stimuli have found that few, if any, PMLS cells are orientation selective. Conversely, studies that have used repetitive stimuli such as gratings have found that most or all PMLS cells are orientation selective. It is not known whether this difference in results is due to the stimuli used or the laboratories using them. The present experiments were designed to answer this question by testing individual PMLS neurons for orientation sensitivity with both bar and grating stimuli. Using quantitative response measures, we found that most PMLS neurons respond well enough to stationary flashed stimuli to use such stimuli to test for orientation sensitivity. On the basis of these tests, we found that about 85% of the cells with well-defined receptive fields are orientation sensitive to flashed gratings, and a similar percentage are orientation sensitive to flashed bars. About 80% of the cells were orientation sensitive to both types of stimuli. The preferred orientations typically were similar for the two tests, and they were orthogonal to the preferred direction of movement. The strength of the orientation sensitivity (measured as the ratio of discharge to the preferred and nonpreferred orientations) was similar to both types of stimuli. However, the width of the orientation tuning curves was systematically broader to bars than to gratings. Several hypotheses are considered as to why previous studies using bars failed to find evidence for orientation sensitivity. In addition, a mechanism for the difference in orientation tuning to bars and gratings is suggested.

Contrast sensitivity was determined for dyslexic and normal readers. When testing with temporally ramped (i.e. stimuli with gradual temporal onsets and offsets) gratings of 0.6, 4.0, and 12.0 cycles/deg, we found no difference in contrast sensitivity between dyslexic readers and controls. Using 12.0 cycles/deg gratings with transient (i.e. abrupt) onsets and offsets, we found that dyslexic individuals had, compared to controls, markedly inferior contrast sensitivity at the shortest stimulus durations (i.e. 17, 34, and 102 ms). This deficit may reflect more sluggish temporal summation. There was no difference in sensitivity to 0.6 cycles/deg gratings with transient onsets and offsets. Under these conditions, the two groups showed a consistent and equal increase in sensitivity relative to the ramped baseline condition at 0.6 cycles/deg at the longer stimulus durations. This demonstrates that dyslexic readers have no deficit in their ability to detect stimulus transients, a finding which appears to be inconsistent with a transient system deficit. That detection of the low-frequency stimuli was mediated by the transient system is further indicated by the fact that these stimuli were more susceptible to forward masking than were the high-frequency stimuli. The effects of masking of both high and low spatial-frequency stimuli were about equal for dyslexic readers and controls. This is not in agreement with the transient system deficit theory, according to which one would expect there to be less masking of high spatial-frequency stimuli in the case of dyslexic readers.

Computer simulations were carried out to evaluate the influence of varying the membrane resistance (Rm) on the dendritic integration capacity of three classes of ganglion cells in the mudpuppy (Necturus maculosus) retina. Three broadly different morphological classes of ganglion cells were selected for this study and represent the range of dendritic tree sizes found in the ganglion cell population of this species. Simulations were conducted on anatomical data obtained from cells stained with horseradish peroxidase; each cell was traced, using a computer as an entry device and later converted to a compartmental (electrical) representation of the cell. Computer-simulation analysis used a time-variant conductance change which was similar in waveform to light-activated bipolar cell input. The simulated membrane resistance for each cell varied between 5000 and 100,000 Ω cm2, and conductance changes were introduced into different regions of the soma-dendritic tree to evaluate dendritic integration efficiency. When higher values of Rm are used, even the largest cells become electrotonically compact and attenuation of voltage responses is minimized from distal to soma regions. Responses were less attenuated from proximal to distal regions of the cell because of the favorable impedance matching, and because less current is required to polarize small “sealed” dendritic terminations. Steady-state responses integrate more effectively than transient responses, particularly when Rm is high, since transient responses were more attenuated by the membrane capacitance. The possibility that Rm is a dynamic property of retinal ganglion cells is discussed in view of the functional organization of dendritic integration efficiency as Rm fluctuates from low to high values.

Starburst amacrine cells in the rabbit retina were labeled following an intraocular injection of the fluorescent dye, 4, 6, diamidino-2-phenylindole (DAPI). From each eye a strip of retina was removed, mounted on a platform beneath an epifluorescence microscope, and superfused with a physiological solution. The tip of a tungsten microelectrode (for extracellular recording) was visually positioned near the cell body of a DAPI-labeled starburst amacrine cell that was located in the ganglion cell layer. Light-evoked responses from the displaced starburst amacrine cells were studied in normal retinas and in retinas that had received a small electrolytic lesion near the optic disk 5–9 months beforehand. In normal retinas, a small spot of light centered over the receptive field of a displaced starburst amacrine cell in nearly all cases evoked a brief burst of spikes only at light onset. When stimulated with a large spot or an annulus of light, many cells gave a small burst of spikes at light offset. In lesioned retinas, the light responses of displaced starburst amacrine cells were recorded in areas of the retina where ganglion cells had degenerated. All cells responded with a large burst of spikes at the onset and offset of a small, centered spot of light. Large spots and annuli of light also evoked robust ON/OFF responses from these cells. The results from this study show that the receptive-field properties of displaced starburst amacrine cells change following axotomy-induced degeneration of ganglion cells. This finding indicates that changes in either synaptic transmission or the membrane properties of neurons occur in the retina following degeneration of ganglion cells.

Enkephalin peptides are present in the retina of several vertebrate species. In the avian retina, enkephalin immunoreactivity is primarily localized to a population of amacrine cells. In the present study, we determined the localization of cells expressing preproenkephalin (PPE) mRNA, which encodes the precursor of enkephalin peptides, in adult as well as in embryonic chicken retinas. The localization of PPE mRNA-expressing cells to the proximal inner nuclear layer (INL) in the adult chicken retina is similar to that of enkephalin-immunoreactive cells observed in previous studies, indicating that amacrine cells expressing PPE mRNA synthesize Met5- and Leu5-enkephalin peptides and related extended forms. Specific hybridization signal is absent in retinas at embryonic day (E) 11, but it is detected in retinas at E 15 and at hatching. PPE mRNA-expressing cells at these ages are located in the proximal INL, and they can be classified as amacrine cells on the basis of their soma size and laminar position. These findings confirm and extend previous observations on the presence of opioid peptides in amacrine cells of the chicken retina. The presence of PPE mRNA at embryonic ages, together with the evidence that enkephalins influence developmental processes, suggests that these peptides modulate retinal maturation in birds.