MacDRP is a Macintosh application that calculates Density Recovery Profiles.

Although the retinotectal projection of goldfish has long been known to have a high degree of retinotopic order, the structural basis for this in terms of the precise positioning of axonal arbors from neighboring retinal ganglion cells has not been determined. In studying this, a small number of neighboring retinal ganglion cells was selectively labeled by a microinjection of DiI into the retina. Following axoplasmic transport for several days, the tectum was removed and flat-mounted for fluorescence microscopy. The injection labeled a small number of axons and their terminal arbors which ranged in size from 108 × 134 μm to 394 × 331 μm with a mean of 233 × 219 μm. This mean size corresponds to about 1/15 of the length of one tectal axis. Although individual arbors labeled from one small retinal injection were always observed near the same retinotopic position, they were almost never coextensive. Overlap between pairs of arbors along the lines of projection perpendicular to the tectal surface averaged 57% of the area of a single arbor. These results indicate that neighboring retinal ganglion cells do not converge onto the same locus but instead project as a continuous retinotopic array of partially overlapping terminal fields.

In a recent study, visual signals were recorded for the first time in starburst amacrine cells of the macaque retina, and, as for mouse and rabbit, a directional bias observed in calcium signals was recorded from near the dendritic tips. Stimulus motion from the soma toward the tip generated a larger calcium signal than motion from the tip toward the soma. Two mechanisms affecting the spatiotemporal summation of excitatory postsynaptic currents have been proposed to contribute to directional signaling at the dendritic tips of starbursts: (1) a “morphological” mechanism in which electrotonic propagation of excitatory synaptic currents along a dendrite sums bipolar cell inputs at the dendritic tip preferentially for stimulus motion in the centrifugal direction; (2) a “space–time” mechanism that relies on differences in the time-courses of proximal and distal bipolar cell inputs to favor centrifugal stimulus motion. To explore the contributions of these two mechanisms in the primate, we developed a realistic computational model based on connectomic reconstruction of a macaque starburst cell and the distribution of its synaptic inputs from sustained and transient bipolar cell types. Our model suggests that both mechanisms can initiate direction selectivity in starburst dendrites, but their contributions differ depending on the spatiotemporal properties of the stimulus. Specifically, the morphological mechanism dominates when small visual objects are moving at high velocities, and the space–time mechanism contributes most for large visual objects moving at low velocities.

We have used light- and electron-microscopic immunohistochemistry to identify the presence of immunoreactivity to neuropeptide Y (NPY) within Müller cells in the retina of the cane toad, Bufo marinus. Müller cells containing NPY-like immunoreactivity (NPY-LI) were identified at the light-microscopic level by the coexistence with immunoreactivity to glial fibrillary acidic protein (GFAP) and at the ultrastructural level by their characteristic relationship to neuron cell bodies and processes. At the light-microscopic level, those cells which contained both NPY-LI and GFAP-LI usually had small cell bodies in the inner nuclear layer, while those cells which contained only NPY-LI were identified as large and small amacrine cells. The radially oriented primary processes in the inner plexiform layer and the vitreal end feet of GFAP-LI Müller cells also expressed NPY-LI. At the ultrastructural level, thin lamellar processes of Müller cells with NPY-LI enclosed some amacrine cell bodies in the inner nuclear layer and amacrine cell dendrites in the inner plexiform layer. These observations suggest that NPY-LI is localized in Müller cells in addition to two types of amacrine cells previously identified in the Bufo retina. This study provides the first evidence that glial elements in the vertebrate retina express NPY-LI.

We examined inward rectification in Limulus ventral photoreceptors using the two-microelectrode voltage clamp. Hyperpolarization in the dark induced an inward current whose magnitude was distinctly dependent on extracellular K+ concentration, [K+0]. The [K+0] dependence resembled the characteristic [K+0] dependence of other inward rectifiers. The inward current was not dependent on extracellular Ca2+ or Na+, and it was unaffected by intracellular injection of Cl−. The hyperpolarization induced currents had two phases, an early nearly instantaneous phase and a slowly developing late phase. The currents were sensitive to extracellular barium and cesium. In voltage-pulse experiments, the magnitudes of the inwardly rectifying currents were variable from cell to cell, with some cells exhibiting negligible inward currents. Large hyperpolarizations (to membrane potentials more negative than about – 140 mV) caused unstable inward current recordings, irreversible desensitization, and irreversible elevation of intracellular Ca2+ concentration. The inward rectifier provides negative feedback by tending to depolarize the cell (with inward current) in response to hyperpolarization. We suggest that the inward rectifier reduces the amount of hyperpolarization that would otherwise be generated by electrogenic processes. This feature would restrict the dynamic voltage range of the photoreceptors at very hyperpolarized potentials.

Isolated retinal rods of the frog consisting of the outer segment and the ellipsoid were patch-clamped and recorded in the whole-cell mode. The recording pipettes were filled with solutions of different composition in order to alter the cytoplasmic content of sodium, phosphate, and calcium ions, and guanine nucleotides. When a simple medium with potassium as the principal cation was used, the dark voltage slowly approached more negative values. This tendency of spontaneous hyperpolarization was reduced significantly when cGMP or GTP were present in the pipette medium. Sodium ions, on the other hand, clearly increased the speed of hyperpolarization. In the presence of sodium (20 mM), the stabilizing effect of GTP did not occur and that of cGMP was clearly diminished. Phosphate (20 mM) neutralized the sodium effect. High calcium levels (100 μM) did not measurably influence the time course of hyperpolarization. We conclude that the normal cytoplasmic sodium level in rods does not exceed 10 mM and that higher internal sodium concentrations interfere with the sodium–calcium exchange mechanism.

Axonal regeneration of retinal ganglion cells (RGCs) into a normal or pre-degenerated peripheral nerve graft after an optic nerve pre-lesion was investigated. A pre-lesion performed 1–2 weeks before a second lesion has been shown to enhance axonal regeneration in peripheral nerves (PN) but not in optic nerves (ON) in mammals. The lack of such a beneficial pre-lesion effect may be due to the long delay (1–6 weeks) between the two lesions since RGCs and their axons degenerate rapidly 1–2 weeks following axotomy in adult rodents. The present study examined the effects of the proximal and distal ON pre-lesions with a shortened delay (0–8 days) on axonal regeneration of RGCs through a normal or pre-degenerated PN graft. The ON of adult hamsters was transected intraorbitally at 2 mm (proximal lesion) or intracranially at 7 mm (distal lesion) from the optic disc. The pre-lesioned ON was re-transected at 0.5 mm from the disc after 0, 1, 2, 4, or 8 days and a normal or a pre-degenerated PN graft was attached onto the ocular stump. The number of RGCs regenerating their injured axons into the PN graft was estimated by retrograde labeling with FluoroGold 4 weeks after grafting. The number of regenerating RGCs decreased significantly when the delay-time increased in animals with both the ON pre-lesions (proximal or distal) compared to control animals without an ON pre-lesion. The proximal ON pre-lesion significantly reduced the number of regenerating RGCs after a delay of 8 days in comparison with the distal lesion. However, this adverse effect can be overcome, to some degree, by a pre-degenerated PN graft applied 2, 4, or 8 days after the distal ON pre-lesion enhanced more RGCs to regenerate than the normal PN graft. Thus, in order to obtain the highest number of regenerating RGCs, a pre-degenerated PN should be grafted immediately after an ON lesion.

Thresholds for the detection of differences in the duration of visual stimuli were determined for a variety of programs of stimulus onset and offset. Performance suffers when a time interval begins with an ON step and ends with another ON stimulus, compared to the standard ON–OFF stimulation, but the decrement is reversed when the light is ramped down to background during the interval. Neither the magnocellular nor the parvocellular streams can be excluded because there is relatively little impairment of duration discrimination when the stimulus has low contrast or is heterochromatic at isoluminance. Performance at a variety of intensity levels suggests that sustained neural firing in an early stage of visual processing provides a background activity, which prevents good temporal precision of signals.

In developing marsupials, the path taken through the optic chiasm by ipsilaterally projecting retinal ganglion cells is complicated. Just prior to entry into the chiasm, ganglion cells destined for the ipsilateral optic tract separate from the remainder of axons by turning abruptly downwards to take a position in the ventral part of the optic nerve. In this report, it is shown that a discrete population of about 10–15 large glial cells transiently form a linear array across the prechiasmatic part of the optic nerve, precisely at this axon turning point. The distinct morphology of these cells and their novel location may reflect a specialized role in axon guidance.

Visual perception is not instantaneous; the perceptual representation of our environment builds up over time. This can strongly affect our responses to visual stimuli. Here, we study the temporal dynamics of visual processing by analyzing the time course of priming effects induced by the well-known Ebbinghaus illusion. In slower responses, Ebbinghaus primes produce effects in accordance with their perceptual appearance. However, in fast responses, these effects are reversed. We argue that this dissociation originates from the difference between early feedforward-mediated gist of the scene processing and later feedback-mediated more elaborate processing. Indeed, our findings are well explained by the differences between low-frequency representations mediated by the fast magnocellular pathway and high-frequency representations mediated by the slower parvocellular pathway. Our results demonstrate the potentially dramatic effect of response speed on the perception of visual illusions specifically and on our actions in response to objects in our visual environment generally.

Cell suspensions of embryonic occipital cortex were transplanted into newborn rats with large unilateral visual cortex lesions. When the animals were adults, they were tested on a difficult visual discrimination, and subsequently their brains were analyzed for possible neurotrophic effects of the transplants on nonvisual cortical areas which normally form connections with the occipital cortex. Behaviorally, animals with lesions and transplants learn to discriminate between columns and rows of squares at a rate which is identical to normal rats while animals with lesions and no transplants are impaired. Volume and cell-density measures show that the transplants also rescue neurons in cortical area 8 that would normally degenerate following the cortical lesion. No such neurotrophic effect of the transplants is found in cortical area 24 or area 17 contralateral to the lesion. In rats with lesions and no transplants, there is a significant correlation between the amount of area 8 remaining after the lesion and trials to criterion on the columns-rows discrimination, a relationship that does not exist in transplant animals because of their normal learning curve and the consistent sparing of area 8. Injections of HRP into the visual cortex contralateral to the lesion result in variable numbers of labeled cells within the transplant. However, there is no consistent relationship between the number of transplant cells which project to the opposite hemisphere and learning of the discrimination. It is suggested that the learning deficit following the lesion is largely attentional and that the sparing of cortical area 8 (which in rats may include the analog of the frontal eye fields present in the primate cortex) contributes to the sparing of function.

Effects of extracellular calcium on signal transmission between photoreceptors and horizontal cells (HCs) are studied in superfused isolated retina of the larval tiger salamander. Horizontal cell light response is optimal when extracellular Ca2+ is maintained between 1–2 mM. Ca2+ levels beyond this range in either direction significantly reduce the HC light response amplitude. When extracellular Ca2+ is lowered from 2 mM to 0.5 mM, the rod input to HCs is reduced whereas the cone input is not affected. In comparison, the peak voltage responses of rods are not changed whereas the cone voltage responses are enhanced in 0.5 mM Ca2+. The selective suppression of rod input to HCs is probably due to the interplay of three factors: (1) the photocurrents, (2) voltage- and time-dependent membrane currents in photoreceptors, and (3) the Ca2-dependent synaptic gain between photoreceptors and HCs.

We studied the correlation between the spatial frequency of complex stimuli and neuronal activity in the monkey inferotemporal (IT) cortex while performing a task that required visual recognition. Single-cell activity was recorded from the right IT cortex. The frequency components of the images used as stimuli were analyzed by using a fast Fourier transform, and a modulus was obtained for 40 spatial frequency ranges from 0.3 to 11.1 cycles/deg. We recorded 82 cells showing statistically significant responses (analysis of variance, P < 0.05) to at least one of the images used as a stimulus. Seventy-eight percent of these cells (n = 64) showed significant responses to at least three images, and in two thirds of them (n = 42), we found a statistically significant correlation (P < 0.05) between cell response and the modulus amplitude of at least one frequency range present in the images. Our results suggest that information about spatial frequency of the visual images is present in the IT cortex.

Termination of GABA signals within the retina occurs through high-affinity reuptake of the released neurotransmitter by GABA transporters (GATs) present in neurons and glia surrounding the release site. In the present work, we have cloned a novel GAT from the retina of the skate (Raja erinacea). The clone codes for a 622 amino acid protein whose sequence has highest similarity to the GABA/β-alanine transporter of the electric ray (Torpedo marmorata) (88% identity) and the GAT-3 isolated from rat brain (75% identity). The protein was expressed in Xenopus oocytes and characterized using the two-electrode voltage-clamp technique. Application of GABA induced a dose-dependent inward current, with 8 μM GABA producing a half-maximal response. The current required the presence of extracellular sodium and was unaffected by the GABA receptor blocker picrotoxin or the GAT-1 specific antagonist NO-711. The high homology between the cloned skate GABA transporter and the GAT-3 equivalents of other species, coupled with the strikingly similar pharmacological profile to GAT-3s of other species, lead us to conclude that we had cloned the GAT-3 homologue for the skate. Polyclonal antibodies specific to GAT-3 and the previously cloned skate GAT-1 transporter were used to examine the distribution of GAT-3 and GAT-1 immunoreactivity in the retina and in isolated cells of the skate. Antibodies for both transporters showed labeling in the outer and inner plexiform layers, and staining extended from the outer to inner limiting membranes. Both GAT-1 and GAT-3 antibodies labeled enzymatically isolated Müller cells, while bipolar cells and horizontal cells did not appear to express either transporter. These results imply that GAT-1 and GAT-3 are both present in Müller cells of the skate retina where they are likely involved in regulating extracellular concentrations of GABA.

The trial-to-trial response variability in sensory cortices and the extent to which this variability can be coordinated among cortical units have strong implications for cortical signal processing. Yet, little is known about the relative contributions and dynamics of defined sources to the cortical response variability and their correlations across cortical units. To fill this knowledge gap, here we obtained and analyzed multisite local field potential (LFP) recordings from visual cortex of turtles in response to repeated naturalistic movie clips and decomposed cortical across-trial LFP response variability into three defined sources, namely, input, network, and local fluctuations. We found that input fluctuations dominate cortical response variability immediately following stimulus onset, whereas network fluctuations dominate the response variability in the steady state during continued visual stimulation. Concurrently, we found that the network fluctuations dominate the correlations of the variability during the ongoing and steady-state epochs, but not immediately following stimulus onset. Furthermore, simulations of various model networks indicated that (i) synaptic time constants, leading to oscillatory activity, and (ii) synaptic clustering and synaptic depression, leading to spatially constrained pockets of coherent activity, are both essential features of cortical circuits to mediate the observed relative contributions and dynamics of input, network, and local fluctuations to the cortical LFP response variability and their correlations across recording sites. In conclusion, these results show how a mélange of multiscale thalamocortical circuit features mediate a complex stimulus-modulated cortical activity that, when naively related to the visual stimulus alone, appears disguised as high and coordinated across-trial response variability.

The effects of cobalt ions on 502-nm rod- and 575-nm cone-driven components of the b-wave of the electroretinogram were studied in the isolated frog retina. Addition of 100–150 μM cobalt initially caused a suppression of rod-driven responses and an enhancement of cone-driven responses. In the continued presence of cobalt, however, the rod-driven responses gradually recovered and the cone-driven responses became suppressed. These concentrations of cobalt had no effect on the rod- and cone-driven mass receptor potentials which were isolated in the presence of 4 mM glutamate. At higher concentrations of cobalt (1 mM or greater), both rod- and cone-driven b-wave responses were eliminated and there was no recovery in the continued presence of cobalt. The results suggest that cobalt has markedly different, time-dependent effects on signal transmission from rods and cones to second-order cells.

An observer locomoting along a straight path sees a pattern of optic flow in which images move approximately radially outward from his heading point. If the observer turns, the optic flow field changes markedly because each object's image now has a component of horizontal motion added to its “optic flow” motion. We tested the responses of 326 cells in the cat's extrastriate area LS (lateral suprasylvian visual area) to movies simulating the optic flow seen during locomotion in a straight line, and during various simulated turns to the left and right. About 60% of 326 cells tested responded to optic flow simulating turns. Of most interest was a subset of cells, 15% of the total, that had “turn-selective” responses. They responded significantly better to turns in a particular direction (usually to the contralateral side) than to turns in the opposite direction or to optic flow simulating straight-ahead locomotion. For each cell, we generated a display of fronto-parallel motion with a direction and speed that matched the image motion in the preferred turn movie, as seen at the receptive-field center. Most turn-selective cells responded significantly better to their preferred turn movie than to this fronto-parallel stimulus. We examined the role of cells' selectivity for stimulus direction, speed, and acceleration in determining cell preference for particular turns. Direction preference played some role for most cells, but about a third of the cells preferred turn movies that did not reflect their direction selectivity. Other factors, including the presence of opposing motion, only rarely appeared to determine cell preferences for particular turn movies.

The inhibition of [3H]acetylcholine (ACh) release from cholinergic amacrine cells by glycine and GABA was studied using an in vivo eyecup preparation in anesthetized rabbits. Glycine (1 mM) had no effect on basal ACh release, but completely blocked the light-evoked release of ACh. Glycine also blocked the strong potentiating effects of picrotoxin (20 μM) normally observed on basal and light-evoked release. Strychnine (20 μM) increased basal release, albeit less than picrotoxin, but partially inhibited and altered the shape of light-evoked responses. Co-perfusion of picrotoxin and strychnine after strychnine application resulted in a larger additional basal increase. However, light-evoked responses were not restored to a control shape and magnitude, or to potentiated levels as with picrotoxin alone, but remained altered and partially inhibited. These results support the concept of a sustained GABA-mediated inhibition of the cholinergic pathway in the intact retina. In contrast, glycine-mediated inhibition of the cholinergic pathway differs, with the present results indicating a significantly smaller sustained inhibition of basal release and a temporal inhibition of light-evoked release. The lack of effect of any of these compounds on kainate-evoked responses indicates that these effects are predominately indirect, possibly on the presynaptic bipolar cell.

Controversy over the relationship between ocular pigmentation and absolute dark-adapted light sensitivity has persisted for over two decades. Previous electrophysiological experiments in hypopigmented mammals (mice, rats, rabbits) show increased thresholds in the dark-adapted state proportional to the deficit in ocular melanin. Animals with the least amount of ocular melanin have the most elevated thresholds. Dark-adapted thresholds in hypopigmented mice show similar threshold elevations in behavioral tests. The present study extends these findings to show that a specific increase in ocular pigmentation results in the converse effect, lowered absolute dark-adapted thresholds. The increase in ocular melanin was accomplished by keeping Himalayan mice in the cold (4°C) for 6 weeks. Himalayan mice (C57BL/6J cH/cH) were compared to black mice (C57BL/6J +/+) and albino mice (C57BL/6J c2J/c2J) after 6 weeks at either 4°C or 20°C in 12-h cycling light (<1 cd/m2). The Himalayan mice that were kept in the cold exhibited a 44% increase in ocular melanin compared to Himalayan mice kept at room temperature. Cold rearing did not effect ocular melanin or visual thresholds in control animals (black mice = 10−5.9 cd/m2 and albino mice = 10−4.4 cd/m2). In contrast, the Himalayan mice maintained at 4°C had thresholds of 10−5.7 cd/m2 compared to 10−5.1 cd/m2 for Himalayan mice kept at 20°C. This represents compelling evidence of a direct relationship between ocular melanin concentration and absolute dark-adapted light sensitivity.

To investigate the physiology and plasticity of mixed rod–cone ON-bipolar cells (Mb) in the goldfish retina, we established a slice preparation which allows us to optically monitor the synaptic activity of bipolar cell axon terminals. We used the styryl dye FM1-43 which is incorporated into active axon terminals due to synaptic vesicle cycling and thus reflects synaptic activity. Different activity states of the axon terminals were revealed when slices prepared from light-adapted retinae were incubated in the presence of FM1-43 under various conditions. Depolarizing high K+ Ringer (50 mM) and the gamma-butyric acid (GABA) antagonist bicuculline (100 μM) resulted in more than two-fold increase in the number of stained terminals compared to slices stained in normal Ringer. In contrast, GABA treatment (0.5 mM) reduced the frequency of stained terminals. Thus, in light-adapted retinal slices the synaptic activity of Mb axon terminals can be modulated towards higher and lower activity states. The fact that the GABA antagonist bicuculline had similar effects as stimulatory high K+ Ringer suggests that inhibitory control is an important component in the regulation of synaptic activity and transmitter release in Mb terminals.