Experiments on the lateral geniculate nucleus (LGN) of the cat based on 14C 2-deoxyglucose (2-DG) autoradiography and intraocular injections of 2-amino-4-phosphonobutyric acid (APB) provided evidence for gradients of metabolic activity in the ON and OFF pathways in layer A, but only very weakly, if at all, in layer Al. Alert and freely moving cats were exposed to square-wave gratings over a 45-min period after injection of the 2-DG. When one eye had been treated previously with APB, contralateral layer A showed a clear gradient of 2-DG label indicating that the remaining OFF pathway was most active ventrally in the layer and, by implication, that the ON pathway is normally most active dorsally. No gradient was apparent in layer Al ipsilateral to the APB eye. Control experiments based on binocular injections of tetrodotoxin (TTX) demonstrated that no gradients were present in the baseline activity within the layers. Finally, monocular injections of TTX provided evidence for gradients of nondominant eye activity in layers A and Al that were maximal near the interlaminar zone between layers A and A1 and declined in mirror-symmetric fashion toward the dorsal border of A and the ventral border of A1.

Combined with earlier anatomical studies showing depth-dependent patterns of geniculo-cortical projection, these results indicate that in the cat, as in several other species, the visual input to striate cortex is partly organized around ON and OFF pathways. In addition, the results suggest that a systematic variation of binocular interaction, perhaps related to ocular dominance, exists through the depths of the geniculate layers. Understanding how the ON and OFF pathways, and binocular interactions, are organized in the thalamus may provide insight into the functional merging of these systems in the cortex.

When a cortical neuron receives synaptic input from both eyes, do the synaptic pathways that mediate the input from each eye match? In this study, inputs from the two eyes were compared by measuring the latencies of EPSPs and IPSPs evoked by electrical stimulation of the two optic nerves. For binocular neurons, these latencies invariably matched closely, indicating that the pathways from the two eyes contain the same number of synapses; monosynaptic input from lamina A of the lateral geniculate nucleus (LGN) is always matched by monosynaptic input from lamina A1. Conversely, polysynaptic input from one eye, either excitatory or inhibitory, is invariably accompanied by similar input from the other eye. In addition, the match between the two eyes in latency indicates that for each eye a synaptic potential is mediated by the same type of afferent, either X or Y.

Judging from intracellular recording, 75% of the neurons studied were binocular, that is, EPSPs could be evoked from either eye. In the remaining 25%, EPSPs could be evoked from only one eye, in agreement with extracellular receptive field studies in which 30% of cortical neurons are monocular.

Tectal evoked potentials (TEPs) in response to sinusoidal gratings of different contrast, spatial and temporal frequency have been recorded from the tectal surface of the pigeon. Responses have been digitally filtered in order to isolate transient oscillatory (fast) potentials (50–150 Hz), transient slow potentials (1–50 Hz), and the steady-state second-harmonic component (16.6 Hz). Transient slow potentials, as well as the steady-state second-harmonic component, are band-pass spatially tuned with a maximum at 0.5 cycles/deg and attenuation at higher and lower spatial frequencies. The high spatial frequency cutoff is 4–5 cycles/deg. Both transient slow potentials and the steady-state second-harmonic component increase in amplitude as a function of log contrast and saturate at about 20% contrast. The contrast sensitivity, as determined by extrapolating TEP amplitude to 0 V is 0.1–0.2%. These characteristics of spatial-frequency selectivity and contrast sensitivity are similar to those reported for single tectal cells. Unlike slow potentials, oscillatory potentials are not band-pass spatially tuned. In addition, their contrast response function does not saturate at moderate contrast. These differences suggest that tectal evoked slow and fast potentials reflect the activity of different neuronal mechanisms.

The mother or daughter of a male with an X-chromosome-linked red/green color defect is an obligate carrier of the color deficient gene array. According to the Lyonization hypothesis, a female carrier's defective gene is expressed and thus carriers may have more than two types of pigments in the L/M photopigment range. An open question is how a carrier's third cone pigment in the L/M range affects the postreceptoral neural signals encoding color. Here, a model considered how the signal from the third pigment pools with signals from the normal's two pigments in the L/M range. Three alternative assumptions were considered for the signal from the third cone pigment: it pools with the signal from (1) L cones, (2) M cones, or (3) both types of cones. Spectral-sensitivity peak, optical density, and the relative number of each cone type were factors in the model. The model showed that differences in Rayleigh matches among carriers can be due to individual differences in the number of the third type of L/M cone, and the spectral sensitivity peak and optical density of the third L/M pigment; surprisingly, however, individual differences in the cone ratio of the other two cone types (one L and the other M) did not affect the match. The predicted matches were compared to Schmidt's (1934/1955) report of carriers' Rayleigh matches. For carriers of either protanomaly or deuteranomaly, these matches were not consistent with the signal from the third L/M pigment combining with only the signal from M cones. The matches could be accounted for by pooling the third-pigment's response with L-cone signals, either exclusively or randomly with M-cone responses as well.

A visual-evoked-potential (VEP) masking technique was used to assess the effects of short- and long-term monocular deprivation on the development of visual inhibitory interactions in kittens. VEP contrast-response curves were recorded in response to contrast-reversed sinusoidal gratings, both with and without superimposed high-contrast masks. The contrast-response curves measured from the nondeprived eye were similar to those of normal cats: with no mask VEP amplitudes increase with contrast up to saturation at about 10% contrast; parallel masks shift the curves to the right, decreasing thresholds; and orthogonal masks decrease the slope of the contrast-response curves without affecting thresholds. After monocular deprivation (either brief or extensive), the contrast-response curves without mask did not show the typical response saturation, and neither parallel nor orthogonal mask had any effect on the contrast-response curves. The masking effects did not return after 100 days of normal vision, although contrast sensitivity and acuity recovered to about half of the normal levels during that period. The results indicate that the inhibitory intracortical circuitry that mediates the orientation-dependent masking effects are highly vulnerable to visual experience.

The discoloration illusion, a new visual phenomenon, is described. This phenomenon originates from the juxtaposition of eight chromatic parallel contours on a white background, creating a luminance gradient and enclosing a light red region. Under these conditions, the inner region appears white: the light red discolors and appears white with both surface color and luminous qualities. In two experiments, the discoloration illusion was (i) compared with the coloration effect of the watercolor illusion, obtained when the number of adjacent contours was reduced to at least two, and (ii) tested under several conditions useful for understanding the roles of the luminance gradient profile. The results suggest that discoloration is not a lightness illusion and does not depend on simultaneous contrast or on achromatic mechanisms, but more likely on chromatic mechanisms that, through the luminance chromatic gradient, provide cues about the interactions of light and surface and model the volume by depicting lights and shades. The discoloration illusion suggests a possible neural scenario where multiple juxtaposed contours may stimulate neurons, selective for different asymmetric luminance profiles and signaling not only the unilateral belongingness of the boundaries and the coloration effect but also the volumetric and the illumination effects.

The color appearance of a physically steady central region can appear to vary over time if a surrounding chromatic light varies in time. The induced temporal variation, however, is strongly attenuated at surround temporal frequencies above ∼3 Hz. At these higher temporal frequencies, the central region appears steady (De Valois et al., 1986). The posited explanation is a cortical low-pass temporal filter. Here, we investigate whether higher temporal-frequency surrounds induce color shifts in the steady appearance of the central test. Surrounds modulated in time along the l or s chromatic direction of MacLeod-Boynton color space were symmetric around equal-energy white (EEW). The temporal frequency of the surround was varied. If observers perceived the central test to be temporally modulating between two points in time, they set two separate matches to the extreme points of this modulation. If the central test appeared steady in time, then color matches were made to this steady appearance. Corroborating previous reports, measurements showed that surround temporal frequencies below ∼3 Hz induced temporal modulation. At higher temporal frequencies, however, the surround induced steady color shifts, compared to a steady surround at its time average (EEW). The measurements imply that a nonlinear neural process affects chromatic induction from time-varying context.

The avian retinotectofugal pathway has been suggested to be homologous to the mammalian retinotectofugal pathway. The projection of the nucleus rotundus upon the ectostriatum is equivalent to that of the pulvinar nucleus upon the extrastriate cortex in mammals. In this system, the optic tectum relays retinal input to the nucleus rotundus, which then ascends to the ectostriatum of the telencephalon. Given the fact that the chick retinotectofugal system becomes mature early during development, the present study attempted to investigate the timecourse of neuronal connections of the embryonic rotundoectostriatal pathway. We used multiple injections of cholera toxin B subunit (CTb) in the ectostriatum of chick embryos to retrogradely trace projections to the nucleus rotundus. We found CTb-labeled neurons in the nucleus rotundus at embryonic day 7.5–8. By embryonic day 8–8.5, increased numbers of CTb-labeled neurons were seen in the nucleus rotundus. It was noted that the time of this initial connection between the nucleus rotundus and the ectostriatum is nearly synchronous with that of the retinotectal and tectorotundal pathways, respectively (Crossland et al., 1975; Thanos & Bonhoeffer, 1987; Wu et al., 2000). These findings, combined with the present study, suggest that the retinotectofugal system becomes established, at least at a structural level, by embryonic day E8.

Activity-dependent synaptic plasticity is characteristic of developing visual systems. Using the frog retinotectal system, we investigated the extent to which afferent input affects neurotransmitter expression in a target structure. We have concentrated on a particular subpopulation of tectal cells that is immunoreactive to substance P (SP). Early in development, SP expression in tectal neurons was restricted to the anterior lateral region of the tectum. As tadpoles developed, this expression expanded into progressively more posterior and medial regions in a manner that closely followed the gradient of tectal maturation. At all times, however, anterior and lateral tectal regions had a greater percent of SP-like immunoreactive (SP-ir) cells than posterior and medial ones. Horseradish peroxidase (HRP) labeling of the retinal ganglion cell projection in conjunction with SP immunocytochemistry demonstrated that innervation by retinal ganglion cell terminals preceded the expression of SP by tectal cells. This suggested that the optic nerve may influence SP differentiation and/or expression. In support of this idea, transection of the optic nerve resulted in a decrease in SP expression in the deafferented tectal lobe of tadpoles. This result, opposite to that seen previously in the adult, also indicates that optic nerve–dependent regulation of SP expression in the developing and mature systems occurs through different pathways.

In contrast to PET and fMRI studies, color-selective responses from the ventro-occipital area have rarely been reported in MEG studies. We tried to minimize the stimulation to all areas in the visual system except the color-processing ones by using a color space based on psychophysical and physiological knowledge in order to maximize the signal-to-noise ratio for MEG responses from the ventro-occipital area. MEG obtained from long intermittent reversals (2.0–3.5 s) of isoluminant chromatic gratings showed two major peaks at the latencies of approximately 100 and 150 ms. The estimated location of the equivalent-current dipole for response at 100-ms latency was in the calcarine sulcus and that of the dipole for the response at 150 ms was in the collateral sulcus in the ventro-occipital area. The response around 150 ms was uniquely observed in MEG elicited by chromatic reversals. The average of lags between MEG responses from the calcarine sulcus and ventro-occipital area was 43 ms, which suggests sequential processing of color information across the visual cortices.

Receptive field organization of cone-driven bipolar cells was investigated by intracellular recording in the intact light-adapted retina of the tiger salamander (Ambystoma tigrinum). Centered spots and concentric annuli of optimum dimensions were used to selectively stimulate the receptive field center and surround with sinusoidal modulations of contrast at 3 Hz. At low contrasts, responses of both the center and surround of both ON and OFF bipolar cells were linear, showing high gain and thus contrast enhancement relative to cones. The contrast/response curves for the fundamental response, measured by a Fast Fourier Transform, reached half maximum amplitude quickly at 13% contrast followed by saturation at high contrasts. The variation of the normalized amplitude of the center and surround responses was remarkably similar, showing linear regression over the entire response range with very high correlations, r2 = 0.97 for both ON and OFF cells. The contrast/response curves of both center and surround for both ON and OFF cells were well fit (r2 = 0.98) by an equation for single-site binding. In about half the cells studied, the nonlinear waveforms of center and surround could be brought into coincidence by scaling and shifting the surround response in time. This implies that a nonlinearity, common to both center and surround, occurs after polarity inversion at the cone feedback synapse. Evidence from paired whole-cell recordings between single cones and OFF bipolar cells suggests that substantial nonlinearity is not due to transmission at the cone synapse but instead arises from intrinsic bipolar cell and network mechanisms. When sinusoidal contrast modulations were applied to the center and surround simultaneously, clear additivity was observed for small responses in both ON and OFF cells, whereas the interaction was strikingly nonadditive for large responses. The contribution of the surround was then greatly reduced, suggesting attenuation at the cone feedback synapse.

The effects of dark adaptation on the response properties of ganglion cells have been documented extensively in the cat retina. To pinpoint the different retinal mechanisms that underlie these effects, we studied the response characteristics of cat horizontal (H) cells during prolonged dark adaptation. H-cell responses were recorded intracellularly in the optically intact, in vivo eye. To disentangle rod and cone contributions, sensitivity changes during dark adaptation were tracked with white light and with monochromatic lights that favored either rod or cone excitation. Stable, long-lasting recordings allowed us to measure changes of sensitivity for adaptation periods up to 45 min. Thresholds for white light and 503-nm monochromatic light decreased steadily and in parallel. The maximum increase of sensitivity, after extinguishing a photopic adaptation light, was 1.8 log units only, reached after about 35 min. Sensitivity for 581-nm lights also increased steadily, but at a shallower slope. The steady increase of sensitivity was concomitant with a linear shift in resting membrane potential and with an increase in relative rod contribution to the threshold responses. Even though small-amplitude responses were rod dominated after prolonged dark adaptation, sensitivity to rod signals remained relatively low, compared to sensitivity of cone responses or to the absolute sensitivity of ganglion cells. This suggests that the cone-H-cell pathway plays no role in the dark-adapted cat retina.

Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (Cm) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging <200 ms. We manipulated Ca2+ influx and the amount of vesicle release by altering the duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels.

The aim of this study was to assess the plasticity of human voluntary fixational eye movement control in relation to visual experience/chronic visual deprivation. Twelve blind adults participated (self-reported vision ≤ light perception in each eye; age range = 23–56 years; visual experience range = 0–28 years; blindness duration range = 6–55 years). Infrared-based recordings of horizontal eye movements were made before, during, and immediately after three 30-s periods of auditory ocular motor feedback, while participants were instructed to look straight ahead and keep their eyes as steady as possible. Percent change in horizontal displacement of the eye during and after feedback was compared with the no-feedback baseline. Eleven of the 12 individuals demonstrated feedback-mediated increase in eye stability, which improved as a function of visual experience. Improved eye stability was inversely related to duration of blindness. Clearly, blind adults can use nonvisual external feedback to stabilize gaze. Thus, the fixational subsystem can exhibit improved voluntary control despite chronic visual deprivation. Possible cortical and subcortical mechanisms are discussed.

It is often assumed that the ultimate goal of a motion-detection system is to faithfully represent the time-dependent velocity of a moving stimulus. This assumption, however, may be an arbitrary standard since the requirements for a motion-detection system depend on the task that is to be solved. In the context of optomotor course stabilization, the performance of a motion-sensitive neuron in the fly's optomotor pathway and of a hypothetical velocity sensor are compared for stimuli as are characteristic of a normal behavioral situation in which the actions and reactions of the animal directly affect its visual input. On average, tethered flies flying in a flight simulator are able to compensate to a large extent the retinal image displacements as are induced by an external disturbance of their flight course. The retinal image motion experienced by the fly under these behavioral closed-loop conditions was replayed in subsequent electrophysiological experiments to the animal while the activity of an identified neuron in the motion pathway was recorded. The velocity fluctuations as well as the corresponding neuronal signals were analyzed with a statistical approach taken from signal-detection theory. An observer scrutinizing either signal performs almost equally well in detecting the external disturbance.

The mammalian retina is known to contain two distinct transducins that interact with their respective rod and cone pigments. However, there are no reports of a nonmammalian species having two distinct transducins. In the present study, we report the cloning and cellular localization of two transducin α subunits (Gαt) from the tiger salamander. Through degenerate polymerase chain reaction (PCR) and subsequent screening of a salamander retina cDNA library, we have identified two forms of Gαt. When compared to existing sequences in GenBank, the cloned subunits showed high similarity to rod and cone transducins. The salamander Gαt-1 has 91.2–93.7% amino acid sequence identity to mammalian rod Gαt subunits and 79.7–80.9% to mammalian cone Gαts. The salamander Gαt-2 has 86.2–87.9% sequence identity to mammalian cone Gαts and 78.9–80.9% to mammalian rod Gαts at the amino acid level. The Gαt-1 cDNA encodes 350 amino acids while the Gαt-2 cDNA encodes 354 residues, which is typical for rod and cone Gαts, respectively, and we thus identified the Gαt-1 as rod and Gαt-2 as cone Gαt. Sequences identified as effector binding sites and GTPase activity regions are highly conserved between the two subunits. Genomic Southern blot analysis showed that rod and cone Gαt subunits are both encoded by single-copy genes. Northern blot analysis identified retina-specific transcripts of 3.0 kb for rod Gαt and 2.6 kb for cone Gαt. Immunohistochemistry in the flat-mounted salamander retina demonstrated that rod Gαt is localized to rods, predominantly in the outer segments; similarly, cone Gαt is localized to cone outer segments. The results confirm that the two sequences encode rod and cone transducins and demonstrate that this lower vertebrate contains two distinct transducins that are localized specifically to rod and cone photoreceptors.

In normal adult cats, a monoclonal antibody directed toward the NR-1 subunit of the N-methyl-d-aspartate (NMDA) receptor (Pharmingen, clone 54.1) produced dense cellular and neuropil labeling throughout all layers of the lateral geniculate nucleus (LGN) and adjacent thalamic nuclei, including the thalamic reticular, perigeniculate, medial intralaminar, and ventral lateral geniculate nuclei. Cellular staining revealed well-defined somata, and in some cases proximal dendrites. NMDAR-1 cell labeling was also evident in the LGN of early postnatal kittens, suggesting that developing LGN cells possess this receptor subunit at or before eye opening. Within the A-layers of the adult LGN, staining encompassed a wide range of soma sizes. Soma size comparisons of NMDAR-1 stained cells with those stained with an antibody directed toward a nonphosphorylated neurofilament protein (SMI-32), which selectively stains Y-relay cells (Bickford et al., 1998), or an antibody to glutamic acid decarboxylase (GAD), which stains for GABAergic interneurons, suggested that NMDA receptors are utilized by relay cells and interneurons. NMDAR-1 staining was also observed in the LGN of cats with early monocular lid suture. Although labeling was apparent in both deprived and nondeprived A-layers of LGN, the distribution of soma sizes was significantly different. In the deprived A-layers of LGN, staining was limited to small- and medium-sized cells. Cells with relatively large soma were lacking. However, cell density measurements as well as soma size comparisons with cells stained for Nissl substance suggested these differences were due to deprivation-induced cell shrinkage and not to a loss of NMDAR-1 staining in Y-cells. Taken together, these results suggest that NMDA receptors are utilized by both relay cells and interneurons in LGN and that alterations in early visual experience do not necessarily affect the expression of NMDA receptors in the LGN.

Efferents from the brain of Limulus course toward its lateral eye and release octopamine and substance P into it. These neurotransmitters have previously been found to act as neuromodulators in this visual system by altering the size of its responses to light. We report here that both also modulate the timing of the receptor potentials (RPs) evoked by brief light flashes and that these timing effects are temperature dependent. Specifically: We extend our previous report that octopamine prolongs ambient RPs in a categorical fashion and here demonstrate that it does the same at colder temperatures. Categorical means that a given RP is either clearly prolonged in a dramatic fashion or its duration is otherwise unremarkable. Octopamine also accelerates the onsets of RPs when they are evoked by weak flashes under cold temperatures. Contrariwise, substance P accelerates RPs at all temperatures and this acceleration dramatically reduces the sluggishness that is otherwise typically present at low temperatures. Quantitative analysis of intensity-response functions also demonstrated that light sensitivity under substance P is significantly augmented. The plain temporal antagonism between these two modulators demonstrates that the visual system of Limulus possesses a well-poised mechanism which could be used to adjust the timing of its neural processing to interface well with the temporal characteristics of those visual stimuli that are currently present.

Stimulation of dark-adapted rods can shift the hues associated with specific wavelengths throughout the spectrum: Rods exert a green bias (strengthen green relative to red) at longer wavelengths and a blue bias (strengthen blue relative to yellow) at short-to-middle wavelengths. A third rod influence at shorter wavelengths is more complicated because it has been shown to reverse direction with change of stimulus duration. Thus, for 30-ms stimuli, rods exert a green bias like that observed at longer wavelengths. However, for 1-s stimuli, rods exert a red bias that is observed nowhere else in the spectrum. We examined the latency (time course) of rod hue biases by measuring the shifts of the three spectral unique hues under dark-adapted versus bleached (cone plateau) conditions. The rod green bias at unique yellow (mean 10 nm) and, in contrast to some prior studies, the rod blue bias at unique green (mean 21 nm) were not systematically affected by test stimulus duration. A quick rod green bias (mean 5 nm) was shown at unique blue for two of three observers but was dominated by a slower rod red bias (mean 11 nm) after 30–50 ms of rod stimulation. These opposing rod influences may reflect competing effects of rod signals on ML-cone and S-cone pathways.

We investigated whether regenerating mature axons recapitulate embryonic features essential to successful reconnectivity within the injured nervous system. Strips from embryonic and adult chick retinae were cultured, and outgrowing axons were examined morphometrically and immunohistochemically. In addition, the target-recognition properties of adult neurites were analyzed. Regenerating adult axons elongate on a poly-L-lysine/laminin substratum with a speed about one order of magnitude slower than that of embryonic axons. Morphologically, adult axonal tips differ dramatically from embryonic growth cones in that they possess only filopodial extensions whereas embryonic growth cones possess both lamellipodial and filopodial processes. Both embryonic and adult neurites express the growth-associated protein GAP-43. When cultured on alternating stripes of anterior and posterior embryonic tectal membranes, both adult and embryonic retinal axons distinguish between the two membrane preparations. Our results demonstrate that during axonal regeneration the mature neurons express embryonic properties that are involved in the recognition of tectal positional cues.