Retino-cortical information transmission achievable with a retina implant

Blind subjects with photoreceptor degeneration perceive phosphenes when their intact retinal ganglion cells are stimulated electrically. Is this approach suitable for transmitting enough information to the visual cortex for partially restoring vision? We stimulated the retina of anesthetized cats electrically and visually while recording the responses in the visual cortex. Transmission of retino-cortical information T was quantified by information theory. T was 20-160 bit/s (per stimulation and recording site) with random electrical or visual impulse stimulation at rates between 20 and 40 s-1. While increasing spatial density of independent electrical stimulation channels T did not saturate with 7 electrodes/mm2 retina. With seven electrodes up to 500 bit/s was transmitted to 15 cortical recording sites. Electrical stimulation basically employs temporal stimulus patterns. They are intimately linked with intensity/contrast information coded by the spike density of retinal ganglion cells. From the cortical information spread we estimated the spatial resolution as 0.5mm cortex corresponding to 0.5-1.0 degrees visual angle. If the human cortex can receive and decode the information transmitted by a retina implant, our quantitative results measured in cats suggest that visuo-motor coordination and object recognition in many in- and out-door situations will be possible.     

The role of the posterior parietal cortex in coordinate transformations for visual-motor integration

Lesion to the posterior parietal cortex in monkeys and humans produces spatial deficits in movement and perception. In recording experiments from area 7a, a cortical subdivision in the posterior parietal cortex in monkeys, we have found neurons whose responses are a function of both the retinal location of visual stimuli and the position of the eyes in the orbits. By combining these signals area 7 a neurons code the location of visual stimuli with respect to the head. However, these cells respond over only limited ranges of eye positions (eye-position-dependent coding). To code location in craniotopic space at all eye positions (eye-position-independent coding) an additional step in neural processing is required that uses information distributed across populations of area 7a neurons. We describe here a neural network model, based on back-propagation learning, that both demonstrates how spatial location could be derived from the population response of area 7a neurons and accurately accounts for the observed response properties of these neurons.     

Rat retinal benzodiazepine receptors are controlled by visual cortical mechanisms

[³H]flunitrazepam binding was assayed in retinae of 25-day-old rats subjected either to unilateral enucleation at day 15, to intracranial unilateral cutting of the optic nerve at day 17, or to unilateral ablation of the visual cortex at day 17 postnatally.Unilateral enucleation resulted in an enhanced [³H]flunitrazepam binding in the retina of the remaining eye by 23% (P < 0.002, two-tailed Student t-test) as compared to unoperated controls.In rats with one optic nerve cut shortly before the optic chiasm, benzodiazepine binding in the retina of the lesioned side was significantly higher by 20.4 ± 7.6% (P < 0.02, N = 10, paired test) in comparison to that in the retina with the intact optic nerve.Unilateral visual cortex ablation resulted in a 13% decrease (P < 0.02) in [³H]flunitrazepam binding in the retina contralateral to the brain lesion.In the lesioned rats of all three groups, the retinal benzodiazepine receptors were no longer capable of being modified by light/dark adaptation as is observed in normal rats. Our data suggest that (i) rat retinal benzodiazepine receptors are under a control from the visual cortex, and (ii) the benzodiazepine receptors of both eyes seem to be mutually tuned, presumably via a cortico-retinal feedback loop and an interhemispheric cortico-cortical information transfer.     

A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements

It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold (“visual acuity”) nor of the contrast threshold (“contrast sensitivity”) of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2-lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1-plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions.     

Position,guidance, and mapping in the developing visual system

Positional identity in the visual system affects the topographic projection of the retina onto its central targets. In this review we discuss gradients and positional information in the retina, when and how they arise, and their functional significance in development. When the axons of retinal ganglion cells leave the eye, they navigate through territory in the central nervous system that is rich in positional information. We review studies that explore the navigational cues that the growth cones of retinal axons use to orient towards their target and organize themselves as they make this journey. Finally, these axons arrive at their central targets and make a precise topographic map of visual space that is crucial for adaptive visual behavior. In the last section of this review, we examine the topographic cues in the tectum, what they are, when, and how they arise, and how retinal axons respond to them. We also touch on the role of neural activity in the refinement of this topography. © 1993 John Wiley & Sons, Inc.     

Functional properties of efferent zones of the motor cortex which project to ipsilateral and contralateral face muscles

In both intact (4 animals) and lesioned (2 preparations with contralateral motor cortex ablation and 1 animal with transection of the rostral two thirds of the corpus callosum) cats, three different types of efferent zones were identified in the face motor cortex by the technique of microstimulation: contralateral, ipsilateral and bilateral efferent zones. The three types of efferent zones had different organizational features such as location, thresholds of effective sites and latencies of motor responses. Mean thresholds of effective sites from ipsilateral and bilateral efferent zones in lesioned animals were not significantly higher than those in intact preparations. In both intact and lesioned animals, neurons endowed with contralateral, bilateral and ipsilateral receptive fields were isolated from the three types of efferent zones.     

Crowding: a cortical constraint on object recognition

The external world is mapped retinotopically onto the primary visual cortex (V1). We show here that objects in the world, unless they are very dissimilar, can be recognized only if they are sufficiently separated in visual cortex: specifically, in V1, at least 6mm apart in the radial direction (increasing eccentricity) or 1mm apart in the circumferential direction (equal eccentricity). Objects closer together than this critical spacing are perceived as an unidentifiable jumble. This is called 'crowding'. It severely limits visual processing, including speed of reading and searching. The conclusion about visual cortex rests on three findings. First, psychophysically, the necessary 'critical' spacing, in the visual field, is proportional to (roughly half) the eccentricity of the objects. Second, the critical spacing is independent of the size and kind of object. Third, anatomically, the representation of the visual field on the cortical surface is such that the position in V1 (and several other areas) is the logarithm of eccentricity in the visual field. Furthermore, we show that much of this can be accounted for by supposing that each 'combining field', defined by the critical spacing measurements, is implemented by a fixed number of cortical neurons.     

Optogenetic Stimulation of the Corticothalamic Pathway Affects Relay Cells and GABAergic Neurons Differently in the Mouse Visual Thalamus

The dorsal lateral geniculate nucleus (dLGN) serves as the primary conduit of retinal information to visual cortex. In addition to retinal input, dLGN receives a large feedback projection from layer VI of visual cortex. Such input modulates thalamic signal transmission in different ways that range from gain control to synchronizing network activity in a stimulus-specific manner. However, the mechanisms underlying such modulation have been difficult to study, in part because of the complex circuitry and diverse cell types this pathway innervates. To address this and overcome some of the technical limitations inherent in studying the corticothalamic (CT) pathway, we adopted a slice preparation in which we were able to stimulate CT terminal arbors in the visual thalamus of the mouse with blue light by using an adeno-associated virus to express the light-gated ion channel, ChIEF, in layer VI neurons. To examine the postsynaptic responses evoked by repetitive CT stimulation, we recorded from identified relay cells in dLGN, as well as GFP expressing GABAergic neurons in the thalamic reticular nucleus (TRN) and intrinsic interneurons of dLGN. Relay neurons exhibited large glutamatergic responses that continued to increase in amplitude with each successive stimulus pulse. While excitatory responses were apparent at postnatal day 10, the strong facilitation noted in adult was not observed until postnatal day 21. GABAergic neurons in TRN exhibited large initial excitatory responses that quickly plateaued during repetitive stimulation, indicating that the degree of facilitation was much larger for relay cells than for TRN neurons. The responses of intrinsic interneurons were smaller and took the form of a slow depolarization. These differences in the pattern of excitation for different thalamic cell types should help provide a framework for understanding how CT feedback alters the activity of visual thalamic circuitry during sensory processing as well as different behavioral or pathophysiological states.     

Characterization of Light Lesion Paradigms and Optical Coherence Tomography as Tools to Study Adult Retina Regeneration in Zebrafish

Light-induced lesions are a powerful tool to study the amazing ability of photoreceptors to regenerate in the adult zebrafish retina. However, the specificity of the lesion towards photoreceptors or regional differences within the retina are still incompletely understood. We therefore characterized the process of degeneration and regeneration in an established paradigm, using intense white light from a fluorescence lamp on swimming fish (diffuse light lesion). We also designed a new light lesion paradigm where light is focused through a microscope onto the retina of an immobilized fish (focused light lesion). Focused light lesion has the advantage of creating a locally restricted area of damage, with the additional benefit of an untreated control eye in the same animal. In both paradigms, cell death is observed as an immediate early response, and proliferation is initiated around 2 days post lesion (dpl), peaking at 3 dpl. We furthermore find that two photoreceptor subtypes (UV and blue sensitive cones) are more susceptible towards intense white light than red/green double cones and rods. We also observed specific differences within light lesioned areas with respect to the process of photoreceptor degeneration: UV cone debris is removed later than any other type of photoreceptor in light lesions. Unspecific damage to retinal neurons occurs at the center of a focused light lesion territory, but not in the diffuse light lesion areas. We simulated the fish eye optical properties using software simulation, and show that the optical properties may explain the light lesion patterns that we observe. Furthermore, as a new tool to study retinal degeneration and regeneration in individual fish in vivo, we use spectral domain optical coherence tomography. Collectively, the light lesion and imaging assays described here represent powerful tools for studying degeneration and regeneration processes in the adult zebrafish retina.     

A spatial property of the retino-cortical mapping

Striate cortex topography derives from a stretching of retinal space along the optic axis. At the retina, relative distances are preserved in a mapping of retinal space onto a spherical surface in the environment. At the cortex, relative distances along visual meridia in the cortical map are preserved in a mapping of striate cortex onto an environmental conic surface whose base is in the plane of the eye. This eco-cortical relationship can be considered a reference frame through which spatial relationships at the cortex might provide information about the environment. The present analysis provides an explanation of changes in cortical magnification with visual eccentricity in the primate and a detailed three-dimensional model of striate topography for the macaque monkey. In man, a conic environmental surface is shown to be uniformly resolvable along meridia in the visual field. Finally, the implications of this analysis of the structural properties of the retino-striate pathway and visual resolution are considered in relation to depth and distance perception.     

Selective disruption of one Cartesian axis of cortical maps and receptive fields by deficiency in ephrin-As and structured activity

The topographic representation of visual space is preserved from retina to thalamus to cortex. We have previously shown that precise mapping of thalamocortical projections requires both molecular cues and structured retinal activity. To probe the interaction between these two mechanisms, we studied mice deficient in both ephrin-As and retinal waves. Functional and anatomical cortical maps in these mice were nearly abolished along the nasotemporal (azimuth) axis of the visual space. Both the structure of single-cell receptive fields and large-scale topography were severely distorted. These results demonstrate that ephrin-As and structured neuronal activity are two distinct pathways that mediate map formation in the visual cortex and together account almost completely for the formation of the azimuth map. Despite the dramatic disruption of azimuthal topography, the dorsoventral (elevation) map was relatively normal, indicating that the two axes of the cortical map are organized by separate mechanisms.     

Brain damage and global stereopsis.

When a single object lies in front of or beyond the plane of fixation its retinal image lies on disparate positions in the two eyes. This 'local' retinal disparity is an excellent cue to depth, and retinal disparties of a few seconds of arc are detectable by people and monkeys. However, most visual scenes produce a complex array of contours in each eye and we can detect the disparity in the arrays despite the ambiguous nature of the disparities, i.e. each contour in one eye could be related to any of several similar contours in the other eye. This ability, known as 'global' stereopsis, may be selectively impaired following brain damage in man. Global stereopsis was measured in rhesus monkeys before and after removing a different cortical visual area in different groups of animals. Only removal of the inferotemporal cortex impaired global stereopsis. The result is related to the findings with human patients and to receptive field properties of neurons in the inferotemporal cortex of monkeys.     

From retinal waves to activity-dependent retinogeniculate map development

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.     

Estimates of underwater and aerial visual acuity in the European beaver <Emphasis Type="Italic">Castor fiber</Emphasis> L. based on morphological data

The eye optics and topographic distribution of ganglion cells were studied using whole mount preparations from European beaver Castor fiber L. The beaver eye optics provides emmetropia in air and hypermetropia in water. The optometrical measurements predict retinal resolution of the beaver eye around 17′ in air and 9′ in water. In air, retinal resolution corresponds to the real visual acuity, whereas in water, visual acuity is below the retinal resolution because of the non-precise focusing.     

Retinal neural progenitors express topographic map markers

Transplantation of neural stem cells for replacing neurons after neurodegeneration requires that the transplanted stem cells accurately reestablish the lost neural circuits in order to restore function. Retinal ganglion cell axons project to visual centers of the brain forming circuits in precise topographic order. In chick, dorsal retinal neurons project to ventral optic tectum, ventral neurons to dorsal tectum, anterior neurons to posterior tectum and posterior neurons to anterior tectum; forming a continuous point-to-point map of retinal cell position in the tectal projection. We found that when stem cells derived from ventral retina were implanted in dorsal host retina, the stem cells that became ganglion cells projected to dorsal tectum, appropriate for their site of origin in retina but not appropriate for their site of implant in retina. This led us to ask if retinal progenitors exhibit topographic markers of cell position in retina. Indeed, retinal neural progenitors express topographic markers: dorsal stem cells expressed more Ephrin B2 than ventral stem cells and, conversely, ventral stem cells expressed more Pax-2 and Ventroptin than dorsal stem cells. The fact that neural progenitors express topographic markers has pertinent implications in using neural stem cells in cell replacement therapy for replacing projecting neurons that express topographic order, e.g., analogous neurons of the visual, auditory, somatosensory and motor systems.     

Two models for transforming auditory signals from head-centered to eye-centered coordinates

Two models for transforming auditory signals from head-centered to eye-centered coordinates are presented. The vector subtraction model subtracts a rate-coded eye position signal from a topographically weighted auditory target position signal to produce a rate-code of target location with respect to the eye. The rate-code is converted into a place-code through a graded synaptic weighting scheme and inhibition. The dendrite model performs a mapping of head-centered auditory space onto the dendrites of eye-centered units. Individual dendrites serve as logical comparators of target location and eye position. Both models produce a topographic map of auditory space in eye-centered coordinates like that found in the primate superior colliculus. Either type can be converted into a model for transforming visual signals from retinal to head-centered coordinates.     

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4gamma, 4delta, 6aalpha, 6agamma, 3a. The lesions were mainly in area 4gamma. In the lesioned hemisphere there were many points around the lesion site (in areas 4gamma and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6agamma) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4gamma, 6agamma and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.     

Source of the eye-movement signal reaching real-motion cells

The stability of visual perception despite eye movements suggests the existence in the visual system of neurons able to recognize whether the movement of a retinal image is due to the actual movement of an object or is self-induced by the ocular movement. We found neurons of this type in several areas of the monkey visual cortex and named them "real-motion" cells. Extracellular recordings were carried out from single neurons of the cortical prestriate area V3A of two awake macaque monkeys. Eighty-seven neurons were studied by comparing their responses during stimulus movement across the stationary receptive field, and receptive-field movement across the stationary stimulus. This visual stimulation was presented against a uniform visual background, in darkness or against a textured background. Neurons which were not real-motion in light (45/87) maintained their behaviour in darkness, while about 40% of real-motion cells lost this behaviour in darkness. Both real-motion and non real-motion cells maintained the same behaviour when tested against a uniform or textured visual background but often, texture increased the difference in the response that real-motion cells showed between stimulus and eye movement. These data suggest that the eye-movement signal which reaches real-motion cells and is responsible for their behaviour may be either retinal or extraretinal in nature. This double innervation is in good agreement with perceptual phenomena related to the detection of movement in the visual field.     

A sparse object coding scheme in area V4

Sparse coding has long been recognized as a primary goal of image transformation in the visual system. Sparse coding in early visual cortex is achieved by abstracting local oriented spatial frequencies and by excitatory/inhibitory surround modulation. Object responses are thought to be sparse at subsequent processing stages, but neural mechanisms for higher-level sparsification are not known. Here, convergent results from macaque area V4 neural recording and simulated V4 populations trained on natural object contours suggest that sparse coding is achieved in midlevel visual cortex by emphasizing representation of acute convex and concave curvature. We studied 165 V4 neurons with a random, adaptive stimulus strategy to minimize bias and explore an unlimited range of contour shapes. V4 responses were strongly weighted toward contours containing acute convex or concave curvature. In contrast, the tuning distribution in nonsparse simulated V4 populations was strongly weighted toward low curvature. But as sparseness constraints increased, the simulated tuning distribution shifted progressively toward more acute convex and concave curvature, matching the neural recording results. These findings indicate a sparse object coding scheme in midlevel visual cortex based on uncommon but diagnostic regions of acute contour curvature.     

Tuning Properties of MT and MSTd and Divisive Interactions for Eye-Movement Compensation

The primate brain intelligently processes visual information from the world as the eyes move constantly. The brain must take into account visual motion induced by eye movements, so that visual information about the outside world can be recovered. Certain neurons in the dorsal part of monkey medial superior temporal area (MSTd) play an important role in integrating information about eye movements and visual motion. When a monkey tracks a moving target with its eyes, these neurons respond to visual motion as well as to smooth pursuit eye movements. Furthermore, the responses of some MSTd neurons to the motion of objects in the world are very similar during pursuit and during fixation, even though the visual information on the retina is altered by the pursuit eye movement. We call these neurons compensatory pursuit neurons. In this study we develop a computational model of MSTd compensatory pursuit neurons based on physiological data from single unit studies. Our model MSTd neurons can simulate the velocity tuning of monkey MSTd neurons. The model MSTd neurons also show the pursuit compensation property. We find that pursuit compensation can be achieved by divisive interaction between signals coding eye movements and signals coding visual motion. The model generates two implications that can be tested in future experiments: (1) compensatory pursuit neurons in MSTd should have the same direction preference for pursuit and retinal visual motion; (2) there should be non-compensatory pursuit neurons that show opposite preferred directions of pursuit and retinal visual motion.