Horizontal cells and cone photoreceptors in the vertebrate retina are interconnected by a complex network of synapses leading to the generation of color-coded responses in chromaticity horizontal cells. A simple cascade model of excitatory feedforward and inhibitory feedback synapses had been suggested to underlie these observations. In this study, the photoresponses of cones and horizontal cells were recorded intracellularly from the turtle eyecup. Three different approaches were adopted in order to test quantitatively the cascade model. Comparing linearity functions between these neurons indicated multiple excitatory inputs to each type of horizontal cells. The depolarizing photoresponses of R/G C-type horizontal cells were considerably faster than those of L-type horizontal cells but slower than those recorded from L-cones. This observation disagrees with the basic assumption of the cascade model that assign the depolarizing photoresponses of R/G C-type horizontal cells to a negative feedback pathway from L-type horizontal cells onto M-cones. Finally, the action spectra of each of the three types of horizontal cells could not be solely accounted for by input from one spectral type of cones. Only by assuming excitatory and inhibitory inputs from all spectral types of cones, the action spectra of all types of horizontal cells could be reconstructed. These findings suggest that the negative feedback pathways from horizontal cells onto cones in the turtle retina cannot solely account for the chromatic properties of the horizontal cells and support a direct inhibitory inputs from cones to turtle horizontal cells.

In this study, we examined functional contributions of major subdivisions of the lateral geniculate nucleus to the cat's lateral suprasylvian visual area (LS) in relation to the patchy horizontal distributions of association inputs. Multiple-unit activity driven via the contralateral eye was assessed during reversible blockade of the retinotopically corresponding part of layer A, the C layers as a group, or the medial interlaminar nucleus (MIN). Inactivating each of these targets reduced activity at some cortical sites, with inactivation of layer A having, on average, the largest effect. Activity was rarely abolished by inactivation of a single target, indicating that most LS sites receive multiple inputs. Dependence on layer A was strongly correlated with the horizontal distribution of association inputs from area 18. Closely spaced injections of anatomical tracers into extensive regions of area 18 resulted in patches of terminal label in lateral suprasylvian cortex. Activity inside the patches was relatively dependent on layer A, whereas that outside the patches was not. Dependence on the MIN and layer A were negatively correlated, suggesting that inputs dominated by the MIN and layer A were concentrated in independent sets of patches. These results indicate that the anatomically observed patchy projections reflect the functional consequences of geniculate lamination. The A layers are high-acuity relays, whereas the MIN is probably a specialization for dim-light vision (Lee et al., 1984; Lee et al., 1992). We propose that the partial overlap of inputs dominated by the A layers and the MIN allows dynamic shifts in their relative contributions to LS responses, optimizing the balance of high-acuity and high-sensitivity channels over a wide range of illumination conditions.

The goal of this study was to determine the effects of inactivating layer A or the C layers of the cat lateral geniculate nucleus on the supragranular layers of area 18, including cells antidromically activated from the lateral suprasylvian visual area (LS). Isolated cells were visually driven via the contralateral eye while the retinotopically corresponding regions of layer A or, in some cases, the C layers were reversibly inactivated with injections of cobaltous chloride. Simple cells were frequently encountered and were on average more dependent upon layer A than were complex cells, a result qualitatively similar to that found previously in area 17 (Malpeli, 1983; Malpeli et al., 1986). However, the influence of the C layers on area 18 was much more apparent than for area 17. In area 18, as in area 17, the dependence of simple cells on particular geniculate layers appears to follow the terminal patterns of the major direct geniculate inputs. Those simple cells most dependent on layer A were located in lower layer 3. Simple cells in upper layer 3, like complex cells, showed little dependence on layer A, but were strongly dependent upon the C layers. All cells antidromically activated from LS were simple cells with rapidly conducting axons. They had, on average, the same moderately strong dependence on layer A as the patches of LS receiving area 18 input (Lee et al., 1997), supporting the conclusion that the influence of layer A in these patches is largely transmitted via association inputs from area 18. These results demonstrate that simple cells play a major role in association pathways.

We characterized the chromatic and temporal properties of a sample of 177 red–green parvocellular neurons in the LGN of Macaca nemestrina, using large-field stimuli modulated along different directions through a white point in color space. We examined differences among the properties of the four subclasses of red–green P-cells (on- and off-center, red and green center). The responses of off-center cells lag the stimulus more than do those of on-center cells. At low temporal frequencies, this causes the phase difference between responses of the two kinds of cells to be considerably less than 180 deg. For isoluminant modulations the phases of on- and off-responses were more nearly 180 deg apart. A cell's temporal characteristics did not depend on the class of cone driving its center. Red center and green center cells have characteristically different chromatic properties, expressed either as preferred elevations in color space, or as weights with which cells combine inputs from L- and M-cones. Red center cells are relatively more responsive to achromatic modulation, and attach relatively more weight to input from the cones driving the center. Off-center cells also attach relatively more weight than do on-center cells to input from the class of cone driving the center.

We studied the interaction between the chromatic and temporal properties of parvocellular (P) neurons in the lateral geniculate nucleus (LGN) of macaque monkeys. We measured the amplitudes and phases of responses to stimulation by spatially uniform fields modulated sinusoidally about a white point in a three-dimensional color space, at a range of temporal frequencies between 1 and 25 Hz. Below about 4 Hz, temporal frequency had relatively little effect on chromatic tuning. At higher frequencies chromatic opponency was weakened in almost all cells. The complex interactions between temporal and chromatic properties are represented by a linear filter model that describes response amplitude and phase as a function of temporal frequency and direction in color space along which stimuli are modulated. The model stipulates the cone inputs to center and surround, their temporal properties, and the linear combination of center and surround signals. It predicts the amplitudes and phases of responses of P-cells, and the change of chromatic properties with temporal frequency. We used the model to investigate whether or not the chromatic signature of the surround in a red–green cell could be estimated from the change in the cell's chromatic properties with temporal frequency. Our findings could be equally well described by mixed cone surrounds as by pure cone surrounds, and we conclude that, with regard to temporal properties, there is no benefit to be gained by segregating cone classes in center and surround.

Photopic electroretinograms (ERGs) elicited by light flashes were recorded for three normal human subjects who were exposed, throughout, to natural ambient light cycles over 24-h day–night periods. ERGs were recorded either with the adaptation state of the eyes maintained at the level set by the natural ambient lighting, or after 10 min dark adaptation. The amplitudes and implicit times of both the a- and b-wave components of the ERG were examined and of these, only the b-wave implicit time exhibited significant diurnal variation, such that the nighttime values were 20–40% greater than those recorded during daytime. Such diurnal variations were observed under both recording conditions and cannot, therefore, be attributed to diurnal changes in the adaptation state of the cone photoreceptors. ERGs were recorded at midday and midnight during 24-h exposure to the natural light cycle, but during the recording period, the short-term adaptation state of the eye was controlled by exposure to rod saturating background field, so that visual sensitivity was the same at both recording times. The b-wave implicit times recorded at midnight were, nonetheless, greater than those recorded at midday. This difference is not, therefore, determined by the short-term state of retinal adaptation, but reflects long-term light history. Measurements performed under 24-h continuous light exposure showed no variation in the b-wave implicit time, whereas some measurements made during extended dark adaptation provided limited evidence for implicit time changes. By controlling the wavelengths to which the eye was exposed during the daylight phase of the diurnal cycle, it was shown that the shifts in b-wave implicit time associated with the change from dark to light are triggered by the rod system, although they are most clearly observed in the cone-dominant responses to long-wavelength light. The results demonstrate a diurnal variation in the temporal responses of the post-photoreceptoral cone pathways of the human retina, which is triggered by activation of the rod photoreceptors.

Patch-clamp and calcium-indicator measurements were used to examine the electrical excitability of large-terminal bipolar neurons from goldfish retina. Large, transient increases in intracellular calcium occurred spontaneously in the synaptic terminal but not in the soma of bipolar neurons. Calcium transients were blocked by hyperpolarization, by external application of calcium-channel blockers, and by the neurotransmitters GABA and glutamate. These observations suggest that calcium action potentials are responsible for the spontaneous increases in intraterminal calcium, which was directly confirmed by electrical recordings of calcium-dependent action potentials in both whole-cell and perforated-patch recordings. We suggest that regenerative depolarization produced by the opening of calcium channels in the synaptic terminal of on-type bipolar neurons represents an amplification mechanism in the high-sensitivity ON pathway in the dark-adapted fish retina.

We studied the GABA sensitivity of horizontal cells in the isolated goldfish retina. After the glutamatergic input to the horizontal cells was blocked with DNQX, GABA depolarized the monophasic and biphasic horizontal cells. The pharmacology of these GABA-induced depolarizations was tested with the GABA receptor antagonists bicuculline-methiodide and picrotoxin, the GABA transporter agonist nipecotic acid, and the GABA transporter antagonist SKF 89976-A. The GABA-induced responses of monophasic horizontal cells consisted of two components; one with characteristics of GABA-gated chloride channels, and one with characteristics of GABA transporters. In biphasic horizontal cells, we only found evidence for GABA-gated chloride channels. The results show that monophasic horizontal cells in goldfish contain the two components of a positive feedback loop (GABA transporters and GABA-gated chloride channels), as described in salamander. Furthermore, our results indicate that the monophasic horizontal cells may project directly to the biphasic horizontal cells, via an excitatory GABAergic pathway. We propose that the function of these GABAergic systems in horizontal cells is to abolish cone dominance in bipolar cells surround in the dark-adapted retina.

The present study has identified a population of cone photoreceptors in the murine retina that are uniquely immunoreactive for protein kinase C (PKC). Wavelength-sensitive cone subtypes are segregated along the dorso-ventral axis in the mouse retina with ventral retina occupied exclusively by ultraviolet wavelength-sensitive (UVWS) cones, and dorsal retina dominated by middle wavelength-sensitive cones. PKC-positive cones are found primarily in the ventral retina, and double-label immunocytochemistry using a short wavelength-sensitive opsin antibody confirms that they specifically correspond to the UVWS cone subtype. The PKC antibody, as documented in other mammals, also identifies rod bipolar cells in the mouse retina. UVWS cones and bipolar cells have previously been shown to share transcriptional regulatory elements, as observed in transgenic mice encoding a portion of the human SWS-opsin promoter controlling the lacZ reporter gene. In such mice, the transgene product, β-galactosidase, is expressed in populations of both cones and bipolar cells. The present study confirms that lacZ-expressing photoreceptors are indeed PKC-positive photoreceptors, but that the lacZ-expressing bipolar cells are not the PKC-positive rod bipolar cells. These cells must correspond to a type of cone bipolar cell.

Macaca mulatta retinas were superfused, in vitro, to measure the efflux of dopamine. Steady light, in the low photopic range, stimulated dopamine release slightly. Flashing light (3 Hz) superimposed over the steady background increased dopamine efflux significantly. This increase was completely blocked by the addition of d,l-2-amino-4-phosphonobutyric acid (d,l-APB, 10–100 μM) to the superfusion medium, but not by the addition of the inactive enantiomer d-APB (10 μM). The results suggest that ON bipolar cells provide the excitatory drive to dopaminergic amacrine cells in primates, as in other species.

The phosphoinositide (PI) intracellular signaling pathway, which triggers Ca2+ release from intracellular stores, appears to be a central feature of phototransduction in most invertebrate species studied. Procedures designed to inhibit PI-pathway reactions cause suppression of excitation to dim lights. However, in Limulus photoreceptors, responses to bright stimuli are in fact enhanced by some of these procedures, suggesting that PI metabolism is not obligatory for light-induced excitation. Other studies, however, suggest that Ca2+ release is obligatory for excitation. We studied this issue by examining the effects of PI-pathway inhibitor, Li+, on electrophysiological responses to light in Limulus photoreceptors. Li+ is reported to cause depletion of intracellular PI-pathway intermediate, inositol; and it offers the pharmacological advantage that its block can be bypassed by introducing exogenous inositol. Introduction of Li+ caused a very slowly developing but complete suppression of responses to dim stimuli. In contrast, Li+ caused a rapidly developing but partial suppression of responses to bright stimuli. Li+-induced suppression was reversed by exogenous introduction of inositol. In addition, inositol prevented Li+-induced suppression of excitation. Li+ enhanced light adaptation (light-induced desensitization) but slowed response deactivation, indicating a difference in the processes underlying these phenomena. Li+ slowed dark adaptation, the recovery of sensitivity following light adaptation. All of these effects were prevented or rescued by extracellularly applied inositol, suggesting the presence of a transmembrane inositol transport system. The overall results suggest that PI-dependent signaling is central and obligatory for excitation in Limulus, at least for responses to dim to moderate illumination. The failure of Li+ to suppress bright light-induced excitation completely may be due to a failure of Li+ to block PI metabolism completely, as in other systems; however, it may point to a parallel, PI-independent excitation pathway possessing very low light sensitivity when PI metabolism is inhibited.

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.

We studied the visuomotor properties of 645 neurons in area 6 of five cats trained in oculomotor tasks. The area we recorded from corresponds well with territories believed to contain the feline homologue of the frontal eye fields observed in primates. Despite an expectation that cells with pre-saccadic activity would be common, only a small fraction (∼5%) of the cells displayed activity that could be linked to subsequent saccadic eye movements. These pre-motor cells appeared to be distributed over a broad region of cortex mixed in with other cell types. As in primates, saccade-related activity tended to occur only during “purposeful” saccades. At least 30% (208/645) of the neurons were visual, with many of these cells possessing huge receptive fields that appeared to include the entire contralateral visual field. Visual responsiveness was generally attenuated by fixation during the oculomotor tasks. Although attentional mechanisms may play a role in this attenuation, this cortical area also exhibits powerful lateral interactions in which spatially displaced visual stimuli suppress each other. Most cells, visually responsive or not, were affected by fixation. Nearly equal proportions of cells showed increases or decreases in activity during fixation. For many of the cells affected by fixation, the source of this modulation appears to reflect cognitive, rather than sensory or motor processes. This included cells that showed anticipatory activity, and cells that responded to the reward only when it was presented in the context of the task. Based on the paucity of pre-saccadic neurons, it would be difficult to conclude that this region of cortex in the cat is homologous to the frontal eye fields of the monkey. However, when considered in the context of differences in the oculomotor habits of these two animals, we believe the homology fits. In addition to pre-motor neurons, the properties of several other cell types found in this area could contribute to the control of gaze.

We studied the visuomotor properties of 54 corticostriatal (CS) and 38 corticotectal (CT) neurons in a region of area 6 that largely corresponds to the cat's frontal eye fields in five cats trained to do simple oculomotor tasks. Overall, these cells were similar to the general population of area 6 neurons described in the previous paper (Weyand & Gafka, 1998), with very few showing pre-saccadic activity. Likewise, CS and CT cells were similar to each other, although only CS cells showed activity exclusively related to the delivery of the reward and CT cells were more likely to be active during saccades. Variability in visual response latencies and the observation that some cells showed initial visual suppression suggest CS and CT cells reflect the output of a variety of intracortical circuits. Despite similar response properties and overlapping laminar origin, CS and CT circuits appear largely independent. Among 32 cells that we could electrically activate (either synaptically or antidromically) from the superior colliculus, only two could also be activated from stimulating electrodes in the striatum. Similarly, 23 of 25 cells electrically activated from the striatum could not be activated from the superior colliculus. Although few of these efferent cells exhibited pre-motor activity, many exhibit properties that could contribute to gaze control.

Recovery from bright light was studied in macaque rods by measuring the membrane current of single outer segments. The recovery phase of some responses displayed a plateau current of about one picoampere lasting for several seconds. The following evidence suggests these “steps” are single photon responses of abnormally long duration. (1) Over a limited range of intensities, step amplitude remained constant and summed linearly with intensity. The collecting area for step generation was about 2.6 × 10−3 μm2. (2) Step duration varied exponentially with a mean duration of about 6.5 s. (3) Fluctuation analysis of the tail currents was consistent with the idea that a step is evoked by isomerization of a single rhodopsin molecule, and that only 1 in 400 isomerizations leads to a response with a step-like waveform. (4) With only the distal portion of the outer segment in the electrode, the polarity of the step response reversed when the proximal portion of the outer segment was illuminated, indicating that step generation results from a local change in outer segment conductance near the site of photon absorption. (5) The probability of eliciting a step varied with the wavelength of light in the manner expected from the absorption spectrum of rhodopsin.

We have reinvestigated receptive-field structure of ganglion cells of the macaque parafovea using counterphase modulation of a bipartite field. Receptive fields were mapped with luminance, chromatic, and cone-isolating stimuli. Center sizes of middle (M) and long (L) wavelength cone opponent cells of the parvocellular (PC) pathway were consistent with previous estimates (Gaussian radii of 2–4 min of arc, corresponding to center diameters of 6–12 min of arc). We calculate that a large factor of the enlargement relative to cone radius could be blur due to the eye's natural optics. Maps were consistent with cone selectivity in surround mechanisms, which had radii of 5–8 min of arc. For magnocellular (MC) cells, center size estimates were also consistent with grating measurements from the literature (also Gaussian radii of 2–4 min of arc). The surround mechanism contributing the MC-cell frequency-doubled response to chromatic modulation appears to possess a subunit structure, and we speculate it derives from nonlinear summation of signals from M,L-cone opponent subunits, such as midget bipolar cells.

We have utilized an associative conditioning paradigm to induce changes in the receptive field (RF) properties of neurons in the adult cat striate cortex. During conditioning, the presentation of particular visual stimuli were repeatedly paired with the iontophoretic application of either GABA or glutamate to control postsynaptic firing rates. Similar paradigms have been used in kitten visual cortex to alter RF properties (Fregnac et al., 1988, 1992; Greuel et al., 1988; Shulz & Fregnac, 1992). Roughly half of the cells that were subjected to conditioning with stimuli differing in orientation were found to have orientation tuning curves that were significantly altered. In general, the modification in orientation tuning was not accompanied by a shift in preferred orientation, but rather, responsiveness to stimuli at or near the positively reinforced orientation was increased relative to controls, and responsiveness to stimuli at or near the negatively reinforced orientation was decreased relative to controls. A similar proportion of cells that were subjected to conditioning with stimuli differing in spatial phase were found to have spatial-phase tuning curves that were significantly modified. Conditioning stimuli typically differed by 90 deg in spatial phase, but modifications in spatial-phase angle were generally 30–40 deg. An interesting phenomenon we encountered was that during conditioning, cells often developed a modulated response to counterphased grating stimuli presented at the null spatial phase. We present an example of a simple cell for which the shift in preferred spatial phase measured with counterphased grating stimuli was comparable to the shift in spatial phase computed from a one-dimensional Gabor fit of the space-time RF profile. One of ten cells tested had a significant change in direction selectivity following associative conditioning. The specific and predictable modifications of RF properties induced by our associative conditioning procedure demonstrate the ability of mature visual cortical neurons to alter their integrative properties. Our results lend further support to models of synaptic plasticity where temporal correlations between presynaptic and postsynaptic activity levels control the efficiency of transmission at existing synapses, and to the idea that the mature visual cortex is, in some sense, dynamically organized.