Showing papers in "Visual Neuroscience in 1995"

Visual latencies in areas V1 and V2 of the macaque monkey

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

Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram.

Abstract: The electroretinogram (ERG) of the dark-adapted cat eye in response to brief ganzfeld flashes of a wide range of intensities was recorded after intravitreal injection of n-methyl DL aspartate (NMDLA, cumulative intravitreal concentration of 1.3-3.9 mM) to suppress inner-retinal components, and after intravitreal DL or L-2-amino-4-phosphonobutyric acid (DL-APB, 1-3 mM; L-APB, 1.2 mM) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX, 40-60 μM), to suppress all post-receptoral neuronal responses. Rod PII, the ERG component arising from rod bipolar cells, was derived by subtracting records obtained after APB and CNQX from post-NMDLA records. When we measured the derived response at fixed times after the stimulus, we found that PII initially increased in proportion to stimulus intensity without any sign of a threshold. The leading edge of PII at early times after the stimulus, when the response was still small, was well described by V(t) = kI(t - t d ) 5 where k is a constant, I is the intensity of the stimulus, and t d is a brief delay of about 3 ms. Correspondingly, the time for the response to rise to an arbitrary small criterion voltage V crit was adequately fitted by t crit = t d + (V crit /kI) 1/5 . The time course of the leading edge of the PII response can be interpreted to indicate that the mechanism generating PII introduces three stages of temporal integration in addition to the three stages that are provided by the mechanism of the rod photoreceptors. This finding is consistent with the operation within the rod bipolar cell of a G-protein cascade similar to that in the rods.

Countermanding saccades in macaque

Abstract: A countermanding paradigm was utilized to investigate the regulation of saccade initiation. Two rhesus monkeys were instructed to generate a saccade to a peripheral target; however, on a fraction of trials after a delay, the monkeys were signaled to inhibit saccade initiation. With short delays between the presentation of the target and the signal to inhibit saccade generation, monkeys withheld saccades to the peripheral target. As the delay of the stop signal increased, monkeys increasingly failed to withhold the saccade. The hypothesis that the generation of the saccade is determined by a race between a go and a stop process provides three explicit means of estimating the covert latency of response to the stop signal. This latency, known as stop signal reaction time, was estimated to be on average 82 ms for both monkeys. Because the stop signal latency represents the time required to exert inhibitory control over saccade production, the countermanding paradigm will be useful for studying neural mechanisms that regulate saccade initiation.

Brightness perception, illusory contours, and corticogeniculate feedback

Abstract: A neural network model is developed to explain how visual thalamocortical interactions give rise to boundary percepts such as illusory contours and surface percepts such as filled-in brightnesses. Top-down feedback interactions are needed in addition to bottom-up feed-forward interactions to simulate these data. One feedback loop is modeled between lateral geniculate nucleus (LGN) and cortical area V1, and another within cortical areas V1 and V2. The first feedback loop realizes a matching process which enhances LGN cell activities that are consistent with those of active cortical cells, and suppresses LGN activities that are not. This corticogeniculate feedback, being endstopped and oriented, also enhances LGN ON cell activations at the ends of thin dark lines, thereby leading to enhanced cortical brightness percepts when the lines group into closed illusory contours. The second feedback loop generates boundary representations, including illusory contours, that coherently bind distributed cortical features together. Brightness percepts form within the surface representations through a diffusive filling-in process that is contained by resistive gating signals from the boundary representations. The model is used to simulate illusory contours and surface brightnesses induced by Ehrenstein disks, Kanizsa squares, Glass patterns, and cafe wall patterns in single contrast, reverse contrast, and mixed contrast configurations. These examples illustrate how boundary and surface mechanisms can generate percepts that are highly context-sensitive, including how illusory contours can be amodally recognized without being seen, how model simple cells in V1 respond preferentially to luminance discontinuities using inputs from both LGN ON and OFF cells, how model bipole cells in V2 with two colinear receptive fields can help to complete curved illusory contours, how short-range simple cell groupings and long-range bipole cell groupings can sometimes generate different outcomes, and how model double-opponent, filling-in and boundary segmentation mechanisms in V4 interact to generate surface brightness percepts in which filling-in of enhanced brightness and darkness can occur before the net brightness distribution is computed by double-opponent interactions.

Receiver operating characteristic (ROC) analysis of neurons in the cat's lateral geniculate nucleus during tonic and burst response mode

Abstract: Relay cells of the lateral geniculate nucleus respond to visual stimuli in one of two modes: burst and tonic. The burst mode depends on the activation of a voltage-dependent, Ca2+ conductance underlying the low threshold spike. This conductance is inactivated at depolarized membrane potentials, but when activated from hyperpolarized levels, it leads to a large, triangular, nearly all-or-none depolarization. Typically, riding its crest is a high-frequency barrage of action potentials. Low threshold spikes thus provide a nonlinear amplification allowing hyperpolarized relay neurons to respond to depolarizing inputs, including retinal EPSPs. In contrast, the tonic mode is characterized by a steady stream of unitary action potentials that more linearly reflects the visual stimulus. In this study, we tested possible differences in detection between response modes of 103 geniculate neurons by constructing receiver operating characteristic (ROC) curves for responses to visual stimuli (drifting sine-wave gratings and flashing spots). Detectability was determined from the ROC curves by computing the area under each curve, known as the ROC area. Most cells switched between modes during recording, evidently due to small shifts in membrane potential that affected the activation state of the low threshold spike. We found that the more often a cell responded in burst mode, the larger its ROC area. This was true for responses to optimal and nonoptimal visual stimuli, the latter including nonoptimal spatial frequencies and low stimulus contrasts. The larger ROC areas associated with burst mode were due to a reduced spontaneous activity and roughly equivalent level of visually evoked response when compared to tonic mode. We performed a within-cell analysis on a subset of 22 cells that switched modes during recording. Every cell, whether tested with a low contrast or high contrast visual stimulus exhibited a larger ROC area during its burst response mode than during its tonic mode. We conclude that burst responses better support signal detection than do tonic responses. Thus, burst responses, while less linear and perhaps less useful in providing a detailed analysis of visual stimuli, improve target detection. The tonic mode, with its more linear response, seems better suited for signal analysis rather than signal detection.

Visual cortex neurons in monkey and cat: effect of contrast on the spatial and temporal phase transfer functions.

Abstract: The responses of simple cells (recorded from within the striate visual cortex) were measured as a function of the contrast and the frequency of sine-wave grating patterns in order to explore the effect of contrast on the spatial and temporal phase transfer functions and on the spatiotemporal receptive field. In general, as the contrast increased, the phase of the response advanced by approximately 45 ms (approximately one-quarter of a cycle for frequencies near 5 Hz), although the exact value varied from cell to cell. The dynamics of this phase-advance were similar to the dynamics of the amplitude: the amplitude and the phase increased in an accelerating fashion at lower contrasts and then saturated at higher contrasts. Further, the gain for both the amplitude and the phase appeared to be governed by the magnitude of the contrast rather than the magnitude of the response. For the spatial phase transfer function, variations in contrast had little or no systematic effect; all of the phase responses clustered around a single straight line, with a common slope and intercept. This implies that the phase-advance was not due to a change in the spatial properties of the neuron; it also implies that the phase-advance was not systematically related to the magnitude of the response amplitude. On the other hand, for the temporal phase transfer function, the phase responses fell on five straight lines, related to the five steps in contrast. As the contrast increased, the phase responses advanced such that both the slope and the intercept were affected. This implies that the phase-advance was a result of contrast-induced changes in both the response latency and the shape/symmetry of the temporal receptive field.

Expression of the proto-oncogene, trk, receptors in the developing rat retina

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

Contrast sensitivity in dyslexia.

Abstract: 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.

Neuronal activity in primate visual cortex assessed by immunostaining for the transcription factor Zif268.

Abstract: 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 4C beta 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.

Organization of the hamster intergeniculate leaflet: NPY and ENK projections to the suprachiasmatic nucleus, intergeniculate leaflet and posterior limitans nucleus.

Abstract: 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.

Simulation of the AII amacrine cell of mammalian retina: functional consequences of electrical coupling and regenerative membrane properties.

Abstract: The AII amacrine cell of mammalian retina collects signals from several hundred rods and is hypothesized to transmit quantal "single-photon" signals at scotopic (starlight) intensities. One problem for this theory is that the quantal signal from one rod when summed with noise from neighboring rods would be lost if some mechanism did not exist for removing the noise. Several features of the AII might together accomplish such a noise removal operation: The AII is interconnected into a syncytial network by gap junctions, suggesting a noise-averaging function, and a quantal signal from one rod appears in five AII cells due to anatomical divergence. Furthermore, the AII contains voltage-gated Na+ and K+ channels and fires slow action potentials in vitro, suggesting that it could selectively amplify quantal photon signals embedded in uncorrelated noise. To test this hypothesis, we simulated a square array of AII somas (Rm = 25,000 Ohm-cm2) interconnected by gap junctions using a compartmental model. Simulated noisy inputs to the AII produced noise (3.5 mV) uncorrelated between adjacent cells, and a gap junction conductance of 200 pS reduced the noise by a factor of 2.5, consistent with theory. Voltage-gated Na+ and K+ channels (Na+: 4 nS, K+: 0.4 nS) produced slow action potentials similar to those found in vitro in the presence of noise. For a narrow range of Na+ and coupling conductance, quantal photon events (approximately 5-10 mV) were amplified nonlinearly by subthreshold regenerative events in the presence of noise. A lower coupling conductance produced spurious action potentials, and a greater conductance reduced amplification. Since the presence of noise in the weakly coupled circuit readily initiates action potentials that tend to spread throughout the AII network, we speculate that this tendency might be controlled in a negative feedback loop by up-modulating coupling or other synaptic conductances in response to spiking activity.

Regional variations in the relative sensitivity to UV light in the mouse retina

Abstract: About 3% of all mouse photoreceptors are cones. An earlier electrophysiological study indicated that there were two classes of cone in the mouse retina having peak sensitivities (lambda max) of about 360 nm and 511 nm. Recent immunocytochemical results show there are two types of cones that have distinctive regional segregation patterns. We used regional stimulation of the retina in conjunction with electroretinogram (ERG) flicker photometry to see if the two cone types identified electrophysiologically are regionalized in a fashion suggested by the anatomical results. We find they are. Relative sensitivity to ultraviolet and visible light stimulation qualitatively parallels that predicted by immunocytochemical labelling. One result of this remarkable regionalization of cone types is that the mouse retina is relatively more sensitive to ultraviolet light stimulation when that light is directed toward the ventral half of the retina.

Temporal and spatial patterns of opsin gene expression in zebrafish (Danio rerio).

Abstract: In zebrafish, the first class of cone photoreceptor to become morphologically distinct is the ultraviolet-sensitive short single cone, at 4 days postfertilization, whereas the last class, the red- and green-sensitive double cone, becomes distinct at 10 days postfertilization. We have examined the time course of visual pigment gene expression in zebrafish using whole-mount in situ hybridization. Within the retina, opsins may be detected as early as 40 h postfertilization with the ultraviolet and rod visual pigments being expressed before the blue- (48 h) and red- (60 h) sensitive pigments. In the pineal, red-sensitive opsin is expressed at 48 h postfertilization. Visual pigment expression provides a useful tool for investigations of early cell fate in zebrafish.

A topographic study of oscillatory potentials in man

Abstract: The purpose of this study was to evaluate the use of slow multifocal m-sequence stimulation in analyzing the topographic distribution and underlying mechanisms (including nonlinearities) of the retinal oscillatory potentials (OPs). In giving us access to the response topography and the nonlinear characteristics of the OPs, the m-sequence technique provides us with two important means for the identification and characterization of the signal sources. In this study, we analyzed the OPs into the first- and second-order components and investigated their topographies and luminance dependence. The distribution of both the first- and second-order OP components differed significantly from that of the flicker ERG investigated by Sutter and Tran (1992). At eccentricities and luminance levels favoring activity by both rods and cones, the second-order OPs were particularly prominent, showing the most clear-defined and complex waveform. The topographic distribution of the second-order OPs showed combined features of both rod and cone distributions. On a strong rod-bleaching background, the second-order OPs were eliminated and the first-order OPs showed a reduced amplitude and a shifted latency. These results are consistent with the notion that the second-order component of the OPs is dominated by contributions from rod-cone interactions.

Regional topography of rod and immunocytochemically characterized "blue" and "green" cone photoreceptors in rabbit retina.

Abstract: Evidence from several sources indicates that the photoreceptors of rabbit retina include rods, green cones and blue cones, and that blue-green color opponency occurs in select retinal ganglion cells. One of us (Famiglietti) has identified wide-field cone bipolar cells as probable blue-cone-selective bipolars, and type C horizontal cells as possibly connected to blue cones. We wished to extend the analysis of blue cone pathways in rabbit retina and to characterize the topographic distribution of blue and green cones. Two monoclonal antibodies raised against chicken visual pigments are reported to label medium- and long-wavelength cones (COS-1) and short-wavelength cones (OS-2) in all mammalian retinas studied thus far (Szel and colleagues). Using selective labeling with these two antibodies and a nonselective method in nasal and temporal halves of the same retinas, we have found that densities of photoreceptors vary systematically, depending upon the size of the eye and age of the animal. In 'standard' New Zealand rabbits of 2-3 kg (2-3 months old), rods reached a peak density of about 300,000/mm2 just dorsal to the visual streak, while cones exhibit peak density at mid-visual streak of about 18,000/mm2. Published measurements of visual acuity in rabbit are less than predicted by this calculation. The ratio of cones to rods is significantly higher in ventral retina, where the density of cones declines to a plateau of 10,000-12,000/mm2, when compared to dorsal retina, where cones are uniformly distributed at a density of about 7000/mm2. The density of OS-2 labeled (presumably "blue") cones is uniformly low, 1000-1500/mm2, in a wide expanse that includes dorsal retina, the visual streak, and much of ventral retina, except for a region of higher density along the vertical midline. We confirm that there is a far ventral horizontal region near the perimeter that is populated exclusively by a high density (about 13,000/mm2) of OS-2-positive cones (Juliusson and colleagues). This region does not extend to the ventral retinal margin, however, where cone density drops precipitously. Transitional zones between COS-1 and OS-2 labeling, in a region of relatively high and uniform cone density, where sums of COS-1 and OS-2 labeling are higher than expected and in which weakly and strongly labeled cones are intermixed, raise questions about the identities of the visual pigment epitopes, the possibility of double labeling, and therefore the possibility of dual expression of pigments in single cones. The "inverted-T-shaped" topography of higher density OS-2 labeling raises doubts about the significance of a ventral concentration of blue cones for visual function in rabbit retina.

Single neurons with both form/color differential responses and saccade-related responses in the nonretinotopic pulvinar of the behaving macaque monkey

Abstract: he nonretinotopic portion of the macaque pulvinar complex is interconnected with the occipitoparietal and occipitotemporal transcortical visual systems where information about the location and motion of a visual object or its form and color are modulated by eye movements and attention. We recorded from single cells in and about the border of the dorsal portion of the lateral pulvinar and the adjacent medial pulvinar of awake behaving Macaca mulatta in order to determine how the properties of these two functionally dichotomous cortical systems were represented. We found a class of pulvinar neurons that responded differentially to ten different patterns or broadband wavelengths (colors). Thirty-four percent of cells tested responded to the presentation of at least one of the pattern or color stimuli. These cells often discharged to several of the patterns or colors, but responded best to only one or two of them, and 86% were found to have statistically significant pattern and/or color preferences. Pattern/color preferential cells had an average latency of 79.1 ± 46.0 ms (range 31-186 ms), responding well before most inferotemporal cortical cell responses. Visually guided and memory-guided saccade tasks showed that 58% of pattern/color preferential cells also had saccade-related properties, e.g. directional presaccadic and postsaccadic discharges, and inhibition of activity during the saccade. In the pulvinar, the mean presaccadic response latency was earlier, and the mean postsaccadic response latency was later, than those reported for parietal cortex. We also discovered that the strength of response to patterns or colors changed depending upon the behavioral setting. In comparison to trials in which the monkey fixated dead ahead during passive presentations of pattern and color stimuli, 92% of the cells showed attenuated responses to the same passive presentation of patterns and colors during fixation when these trials were interleaved with trials which also required active saccades to pattern and color targets in the periphery. We conclude that properties which represent the functionally dichotomous object and spatial visual systems are found together in single pulvinar neurons and that the responses of these cells to pattern or color stimuli are influenced by the focus of spatial attention. The pulvinar is the first structure in the brain shown to have neurons which integrate both object and spatial properties and the response latencies indicate that this information is processed before that in cortex. These results are discussed in terms of role of the pulvinar in visual attention as well as its unique role in providing both object feature and spatial location information to the inferotemporal cortex (... marie antoinette...) The outer plexiform layer of the retina contains a neural circuit in which cone synaptic terminals are electrically coupled and release glutamate onto wide-field and narrow-field horizontal cells. These are also electrically coupled and feed back through a GABAergic synapse to cones. In cat this circuit's structure is known in some detail, and much of the chemical architecture and neural responses are also known, yet there has been no attempt to synthesize this knowledge. We constructed a large-scale compartmental model (up to 50,000 compartments) to incorporate the known anatomical and biophysical facts. The goal was to discover how the various ci

A comparison of receptive field and tracer coupling size of horizontal cells in the rabbit retina

Abstract: The large receptive fields of retinal horizontal cells are thought to reflect extensive electrical coupling via gap junctions. It was shown recently that the biotinylated tracers, biocytin and Neurobiotin, provide remarkable images of coupling between many types of retinal neuron, including horizontal cells. Further, these demonstrations of tracer coupling between horizontal cells rivaled the size of their receptive fields, suggesting that the pattern of tracer coupling may provide some index of the extent of electrical coupling. We studied this question by comparing the receptive field and tracer coupling size of dark-adapted horizontal cells recorded in the superfused, isolated retina-eyecup of the rabbit. Both the edge-to-edge receptive field and space constants (lambda) were computed for each cell using a long, narrow slit of light displaced across the retinal surface. Cells were subsequently labeled by iontophoretic injection of Neurobiotin. The axonless A-type horizontal cells showed extensive, homologous tracer coupling in groups greater than 1000 covering distances averaging about 2 mm. The axon-bearing B-type horizontal cells were less extensively tracer coupled, showing homologous coupling of the somatic endings in groups of about 100 cells spanning approximately 400 microns and a separate homologous coupling of the axon terminal endings covering only about 275 microns. Moreover, we observed a remarkable, linear relationship between the size of the receptive fields of each of the three horizontal cell endings and the magnitude of their tracer coupling. Our findings suggest that the extent of tracer coupling provides a strong, linear index of the magnitude of electrical current flow, as derived from receptive-field measures, across groups of coupled horizontal cells. These data thus provide the first direct evidence that the receptive-field size of horizontal cells is related to the extent of their coupling via gap junctions.

Dynamics of the orientation tuning of postsynaptic potentials in the cat visual cortex

Abstract: We evaluated the dynamic aspects of the orientation tuning of the input to cat visual cortical neurons by analyzing the postsynaptic potentials (PSPs) evoked by flashing bars of light. The PSPs were recorded using in vivo whole-cell technique, and we analyzed the orientation tuning during subsequent temporal windows after stimulus onset and offset. Our results show that the amplitudes of the postsynaptic potential are reliably tuned to orientation and matching that of the spike responses only during certain temporal windows. During the first 100 ms after stimulus presentation, orientation tuning of the membrane potential underwent regular changes. Within particular intervals, orientation tuning of the input was much sharper than that estimated according to the whole response. In most cells, optimal orientation was usually stable over the whole period. In several cells which had a second hump of EPSPs in the response, this second hump was tuned to the same orientation as the first one, but always showed sharper tuning. Estimation of the integration time revealed sufficient delay between the appearance of EPSPs and spikes, to let inhibition influence spike generation. These results show that orientation selectivity of the input to cortical cells is a dynamic function, and also indicate the possibility of temporal coding in the visual system.

How task-related are the responses of inferior temporal neurons?

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

Co-stratification of GABAA receptors with the directionally selective circuitry of the rat retina.

Abstract: Direction-selective (DS) ganglion cells of the mammalian retina have their dendrites in the inner plexiform layer (IPL) confined to two narrow strata. The same strata are also occupied by the dendrites of cholinergic amacrine cells which are probably presynaptic to the DS ganglion cells. GABA is known to play a crucial role in creating DS responses. We examined the types of GABAA receptors expressed by the cholinergic amacrine cells and also those expressed by their presynaptic and postsynaptic neurons, by applying immunocytochemical markers to vertical sections of rat retinas. Double-labelling experiments with antibodies against choline acetyltransferase (ChAT) and specific antibodies against different GABAA receptor subunits were performed. Cholinergic amacrine cells seem to express an unusual combination of GABAA receptor subunits consisting of alpha 2-, beta 1-, beta 2/3-, gamma 2-, and delta-subunits. Bipolar cells, which could provide synaptic input to the DS circuitry, were stained with antibodies against the glutamate transporter GLT-1. The axon terminals of these bipolar cells are narrowly stratified in close proximity to the dendritic plexus of displaced cholinergic amacrine cells. The retinal distribution of synaptoporin, a synaptic vesicle associated protein, was studied. Strong reduction of immunolabelling was observed in the two cholinergic strata. The anatomical findings are discussed in the context of models of the DS circuitry of the mammalian retina.

Organization of ocular dominance and orientation columns in the striate cortex of neonatal macaque monkeys.

Abstract: Previous work has shown that small, stimulus-dependent changes in light absorption can be used to monitor cortical activity, and to provide detailed maps of ocular dominance and optimal stimulus orientation in the striate cortex of adult macaque monkeys (Blasdel & Salama, 1986; Ts'o et al., 1990). We now extend this approach to infant animals, in which we find many of the organizational features described previously in adults, including patch-like linear zones, singularities, and fractures (Blasdel, 1992b), in animals as young as 3 1/2 weeks of age. Indeed, the similarities between infant and adult patterns are more compelling than expected. Patterns of ocular dominance and orientation, for example, show many of the correlations described previously in adults, including a tendency for orientation specificity to decrease in the centers of ocular dominance columns, and for iso-orientation contours to cross the borders of ocular dominance columns at angles of 90 deg. In spite of these similarities, there are differences, one of which entails the strength of ocular dominance signals, which appear weaker in the younger animals and which increase steadily with age. Another, more striking, difference concerns the widths of ocular dominance columns, which increase by 20% during the first 3 months of life. Since the cortical surface area increases by a comparable amount, during the same time, this 20% expansion implies that growth occurs anisotropically, perpendicular to the ocular dominance columns, as the cortical surface expands. Since the observed patterns of orientation preference expand more slowly, at approximately half this rate, these results also imply that ocular dominance and orientation patterns change their relationship, and may even drift past one another, as young animals mature.

Contrast coding by cells in the cat's striate cortex: monocular vs. binocular detection.

Abstract: 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.

Activity correlates of cytochrome oxidase-defined compartments in granular and supragranular layers of primary visual cortex of the macaque monkey.

Abstract: To determine if changes in metabolic capacity revealed by cytochrome oxidase (CO) histochemistry are related to sustained changes in energy-utilizing neuronal activity, we assayed CO levels and recorded multiunit firing rates along nearly tangential penetrations of V1 in seven adult macaque monkeys before and after single, monocular injections of TTX Within as little as 14 h, TTX blockade began to reduce CO staining in zones of layer 4C that received dominant input from the injected eye Since simple monocular occlusion has only minor effects on cortical CO levels (Trusk et al, 1990), the changes in activity that were specifically associated with CO depletion were isolated by comparing spike rates during monocular TTX blockade and during monocular occlusion Five second samples of multiunit spike rate were obtained after 2-min adaptation to each of four adapting fields: black, gray, white, and textured Results were similar for these four conditions In layer 4C, ocular dominance zones with input from the TTX eye had ongoing spike rates that were 48% of the rates in zones with input from a normal but occluded eye In six animals, it was possible to record activity at a single site before, during, and after the onset of TTX blockade Background activity at these interpuff sites decreased as much as 3-fold in less than 1 h but stabilized within 3–4 h to an average of 53% of pre-TTX rates These data support the interpretation that energy utilization linked to sustained spike rates partially regulates CO levels under normal conditions, at least in layer 4 Furthermore, changes in neuronal activity induced by retinal TTX preceded the detectable reduction in CO activity in V1 suggesting that the adjustment of CO levels was in response to the altered activity

Simulation of an anatomically defined local circuit: the cone-horizontal cell network in cat retina.

Abstract: The outer plexiform layer of the retina contains a neural circuit in which cone synaptic terminals are electrically coupled and release glutamate onto wide-field and narrow-field horizontal cells. These are also electrically coupled and feed back through a GABAergic synapse to cones. In cat this circuit's structure is known in some detail, and much of the chemical architecture and neural responses are also known, yet there has been no attempt to synthesize this knowledge. We constructed a large-scale compartmental model (up to 50,000 compartments) to incorporate the known anatomical and biophysical facts. The goal was to discover how the various circuit components interact to form the cone receptive field, and thereby what possible function is implied. The simulation reproduced many features known from intracellular recordings: (1) linear response of cone and horizontal cell to intensity, (2) some aspects of temporal responses of cone and horizontal cell, (3) broad receptive field of the wide-field horizontal cell, and (4) center-surround cone receptive field (derived from a "deconvolution model"). With the network calibrated in this manner, we determined which of its features are necessary to give the cone receptive field a Gaussian center-surround shape. A Gaussian-like center that matches the center derived from the ganglion cell requires both optical blur and cone coupling: blur alone is too narrow, coupling alone gives an exponential shape without a central dome-shaped peak. A Gaussian-like surround requires both types of horizontal cell: the narrow-field type for the deep, proximal region and the wide-field type for the shallow, distal region. These results suggest that the function of the cone-horizontal cell circuit is to reduce the influence of noise by spatio-temporally filtering the cone signal before it passes through the first chemical synapse on the pathway to the brain.

Effects of wavelength on the timing and laminar distribution of illuminance-evoked activity in macaque V1

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

Two signals in the human rod visual system: a model based on electrophysiological data.

Abstract: In the human rod visual system, self-cancellation of flicker signals is observed at high rod intensity levels near 15 Hz, both perceptually and in the electroetinogram (ERG). This and other evidence suggests that two rod signals are transmitted through the human retina with different speeds of transmission. Here we report a series of flicker ERG recordings from a normal observer and an observer who lacks cone vision. From these results, we propose a quantitative model of the two rod signals, which assumes (1) that the amplitude of the slow signal grows linearly with log intensity but then saturates at approximately 1 scot. td; (2) that the amplitude of the fast signal grows linearly with intensity; (3) that there is a difference in time delay of approximately 33 ms between two rod signals of the same polarity (or of approximately 67 ms if the signals are of inverted polarity); and (4) that the time delay of both signals declines linearly with log intensity (by approximately 10 ms per log scot. td). These simple assumptions provide a remarkably good account of the experimental data. Our results and model are relevant to current anatomical theories of the mammalian rod visual system. We speculate that the slower signal in the human ERG may reflect the transmission of the rod response via the rod bipolars and the AII amacrine cells, while the faster signal may reflect its transmission via the rod-cone gap junctions and the cone bipolars. There are, however, several objections to this simple correspondence.

Interlaminar connections of the superior colliculus in the tree shrew. II: Projections from the superficial gray to the optic layer.

Abstract: This study of the tree shrew, Tupaia belangeri, provides evidence for an intracollicular pathway that arises in the superficial gray layer and terminates in the optic layer. As a first step, Nissl, myelin, and cytochrome oxidase stains were used to identify the layers of the superior colliculus in the tree shrew. Second, anterograde and retrograde axonal transport methods were used to determine relationships between laminar borders and patterns of connections. Intraocular injections of wheat germ agglutinin conjugated to horseradish peroxidase showed that the border between the superficial gray and optic layers in the tree shrew is marked by a sharp decrease in the density of retinotectal projections. The optic layer also could be distinguished from the subjacent intermediate gray layer by differences in connections. Of the two layers, only the intermediate gray layer received projections following injections of wheat germ agglutinin conjugated to horseradish peroxidase within substantia nigra pars reticulata. Similarly, following injections of horseradish peroxidase or biocytin in the paramedian pons, the intermediate gray but not the optic layer contained labeled cells of origin for the main premotor pathway from the tectum, the predorsal bundle. Next, cells in the superficial gray layer were intracellularly injected with biocytin in living brain slices. Axons were traced from narrow and wide field vertical cells in the deep part of the superficial gray layer to the gray matter surrounding the fiber fascicles of the optic layer. Small extracellular injections of biocytin in brain slices showed that the optic layer gray matter contains a population of stellate cells that are in position to receive the input from the superficial layer. Finally, small extracellular injections of biocytin in the intermediate gray layer filled cells that sent prominent apical dendrites into the optic layer, where they may be directly contacted by the superficial gray layer cells. Taken together, the results support the hypothesis that the optic layer is functionally distinct from its adjacent layers, and may provide a link in the transfer of information from the superficial, retinal recipient, to the intermediate, premotor, layer of the superior colliculus.

Photoreceptors in a primitive mammal, the South American opossum, Didelphis marsupialis aurita: Characterization with anti-opsin immunolabeling

Abstract: The retinas of placental mammals appear to lack the large number and morphological diversity of cone subtypes found in diurnal reptiles. We have now studied the photoreceptor layer of a South American marsupial (Didelphis marsupialis aurita) by peanut agglutinin labeling of the cone sheath and by labeling of cone outer segments with monoclonal anti-visual pigment antibodies that have been proven to consistently label middle-to-long wavelength (COS-1) and short-wavelength (OS-2) cone subpopulations in placental mammals. Besides a dominant rod population (max. = 400,000/mm2) four subtypes of cones (max. = 3000/mm2) were identified. The outer segments of three cone subtypes were labeled by COS-1: a double cone with a principal cone containing a colorless oil droplet, a single cone with oil droplet, and another single cone. A second group of single cones lacking oil droplets was labeled by OS-2 antibody. The topography of these cone subtypes showed striking anisotropies. The COS-1 labeled single cones without oil droplets were found all over the retina and constituted the dominant population in the area centralis located in the temporal quadrant of the upper, tapetal hemisphere. The population of OS-2 labeled cones was also ubiquitous although slightly higher in the upper hemisphere (200/mm2). The COS-1 labeled cones bearing an oil droplet, including the principal member of double cones, were concentrated (800/mm2) in the inferior, non-tapetal half of the retina. The two spectral types of single cones resemble those of dichromatic photopic systems in most placental mammals. The additional set of COS-1 labeled cones is a distinct marsupial feature. The presence of oil droplets in this cone subpopulation, its absence in the area centralis, and the correlation with the non-tapetal inferior hemisphere suggest a functional specialization, possibly for mesopic conditions. Thus, sauropsid features have been retained but probably with a modified function.

The morphology of the dorsal eye of the hydrothermal vent shrimp, Rimicaris exoculata.

Abstract: The bresiliid shrimp, Rimicaris exoculata, lives in large masses on the sides of hydrothermal vent chimneys at two sites on the Mid-Atlantic Ridge. Although essentially no daylight penetrates to depths of 3500 m, very dim light is emitted from the hydrothermal vents themselves. To exploit this light, R. exoculata has evolved a modified compound eye on its dorsal surface that occupies about 0.5% of the animal's body volume. The eye's morphology suggests that it is extremely sensitive to light. The cornea of the dorsal eye is smooth with no dioptric apparatus. The retina consists of two wing-shaped lobes that are fused across the midline anteriorly. The rhabdomeral segments of the 7000 ommatidia form a compact layer of photosensitive membrane with an entrance aperture of more than 26 mm2. Within this layer, the volume density of rhabdom is more than 70%. Below the rhabdomeral segments, a thick layer of white diffusing cells scatters light upward into the photoreceptors. The arhabdomeral segments of the five to seven photoreceptors of each ommatidium are mere strands of cytoplasm that expand to accommodate the photoreceptor nuclei. The rhabdom is comprised of well-organized arrays of microvilli, each with a cytoskeletal core. The rhabdomeral segment cytoplasm contains mitochondria, but little else. The perikaryon contains a band of mitochondria, but has only small amounts of endoplasmic reticulum. There is no ultrastructural indication of photosensitive membrane cycling in these photoreceptors. Vestigial screening pigment cells and screening pigment granules within the photoreceptors are both restricted to the inner surface of the layer of the white diffusing cells. Below the retina, photoreceptor axons converge in a fan-shaped array to enter the dorsal surface of the brain. The eye's size and structure are consistent with a role for vision in shrimp living at abyssal hydrothermal vents.

Calbindin D-28K immunoreactivity of human cone cells varies with retinal position

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