Retinotopic Projection Research Articles

The topographic relationship between shifting binocular maps in the developing dorsal lateral geniculate nucleus

The major mammalian subcortical visual structures receive topographically ordered projections from both eyes. In the adult dorsal lateral geniculate nucleus (dLGN) each projection terminates in separate restricted regions of the nucleus. This pattern is different during development. Initially in ferrets the projections from each eye to the dLGN overlap throughout this structure. Although the projections do not occupy regions that are appropriate given the adult pattern, they are both retinotopically organised. Consequently, the formation of the adult pattern requires that the two retinotopic projections shift in relation to one another. The experiments undertaken here on the newborn ferret demonstrate the relationship between the two unsegregated projections in terms of their retinal origin and relative pattern of projection to the dLGN. By establishing the relationship between the projections at this stage of development it is possible to determine the relative changes that must be made between them in order to bring about the adult pattern of registration. By mapping the two unsegregated projections with a combination of retinal lesions and anterograde tracing methods it is demonstrated that at birth the ipsilateral projection arises from the temporal retina, and the contralateral projection arises from the entire retina. Because of the significant contralateral projection from the temporal retina the relatively sharp nasotemporal division found in the adult is not present at this stage. This element of the contralateral projection maps in continuity with the rest of this projection and terminates at the caudal pole of the nucleus. However, it is probably lost before the adult pattern has clearly started to develop.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological recovery of axotomized goldfish retinal ganglion cells in an environment known to prevent retinotopic refinement of their regenerated tectal arbors

Axonal injury provokes well-characterized morphological changes in goldfish retinal ganglion cells. These reach a peak as the regenerating axons restore a grossly retinotopic projection map to the tectum, and then regress as the map is refined by a mechanism involving locally-correlated activity. The aim of this study was to look for any interdependence between morphological recovery and retinotopic refinement. Stroboscopic light was used to keep regenerated optic arbors in non-retinotopic locations for 70 days after optic nerve cut and lens ablation. Control were kept in constant or diurnal light, both of which allow refinement of the retinotectal map. Nucleolar frequency, perikaryal area and nuclear area were used as indices of neuronal recovery, and ganglion cell counts were performed. After 35 days in diurnal light, the nucleoli of axotomized cells had increased in size, prominence and number, and both nucleus and cytoplasm had roughly doubled in area. After 70 days, these features had almost returned to normal not only in diurnal and constant light but in stroboscopic light as well. A small but significant cell loss, averaging 13.4–14.7%, was seen after optic nerve cut and lens ablation regardless of stage in regeneration (35 or 70 days) or lighting. Evidently, morphological recovery is independent of retinotopic refinement, which is known to be no further advanced after 70 days in stroboscopic light than after 35 days in diurnal light.

Goldfish retinal axons respond to position-specific properties of tectal cell membranes in vitro

Using a special in vitro assay, we tested whether retinal ganglion cell axons in an adult vertebrate, the goldfish (which can regenerate a retinotopic projection after optic nerve section), recognize position-specific differences in cell surface membranes of their target, the tectum opticum. On a surface consisting of alternating stripes of membranes from rostral and caudal tectum, temporal axons accumulate on membranes derived from their retinotopically related rostral tectal half. Nasal axons grow randomly over both types of membranes. Nasal and temporal axons can elongate on both rostral and caudal membranes. A quantitative growth test, however, revealed that caudal membranes are less permissive substrates for the outgrowth of temporal axons than rostral membranes, and than rostral or caudal membranes for nasal axons.

The locus of optic nerve head representation in the retinotopic projection over nucleus geniculatus lateralis ventralis and nucleus griseum tectalis in the chick also lacks a retinal projection.

Recently we have demonstrated the presence of a gap in the avian retinotectal projection, that corresponds with the locus of retinotopic representation of the elongated optic nerve head. The present report describes an equivalent gap in the optic neuropiles of the avian ventral geniculate nucleus and griseum tectalis formation, detected after filling optic terminals anterogradely from the contralateral eye with peroxidase. A projection-less strip appears at the expected retinotopic position in both grisea intersecting radially all the strata of the corresponding neuropiles. It is speculated that a common synaptogenetic mechanism must account for these gaps.

Compression and expansion without impulse activity in the retinotectal projection of goldfish.

The capacity of regenerating optic fibers to undergo retinotopic compression and expansion in the absence of impulse activity was tested by eliminating activity with periodic intraocular injections of tetrodotoxin (TTX) during regeneration. To test for compression, the posterior half of tectum was removed and the optic nerve crushed. For expansion, the temporal half of retina was ablated and the nerve also crushed. The projection was then subsequently examined with electrophysiological mapping and autoradiographic tracing. Like electrically active fibers, silent fibers formed a retinotopically ordered projection that was compressed onto the anterior half tectum. Similarly, TTX-treated fibers from a nasal half retina formed a retinotopic projection that was expanded across the entire tectum. Except for some enlargement of receptive fields produced by the TTX, the topography was equivalent to that formed by active fibers. Thus, fibers can apparently maintain relative positions irrespective of absolute tectal position without the benefit of activity-dependent ordering. This implies the existence of an activity-independent mechanism for relative positioning that may operate across larger distances than the activity-dependent ordering responsible for fine topography and ocular dominance columns.

Regenerating retinal fibers of the goldfish make temporary and unspecific but functional synapses before forming the final retinotopic projection

Many investigators have examined the retinotectal projection following regeneration, but the mapping technique used in these studies mainly involved recording action potentials from presynaptic terminals. Hence it was not possible to analyse the postsynaptic phenomena underlying the target finding process of the retinal fibers. In the present study, the process of making functional synapses was examined using field potentials generated by small spots of light fixed in the visual field. The results show that regenerating retinal fibers first make functional but temporary, unspecific and diffuse synapses before reaching the target area to form a sharpened retinotopic projection. It is suggested that the formation of synapses subserves an important role in the target finding process.

Axonal arborization in the developing chick retinotectal system.

The growth and arborization of chicken retinal ganglion cell axons have been investigated by means of an intraaxonally transported fluorescent marker in the developing retinotectal system. The fluorescent dye D282 or diI from the carbocyanine group of dyes is taken up by ganglion cells and labels the axon as well as the axonal growth cones and the terminal arborizations on the tectum. Branching and arborization start in the chick retinotectal system on embryonic day 9 (E9). At this stage retinal axons leave the stratum opticum (SO) and invade the stratum griseum et fibrosum superficiale (SGFS), where arborization takes place. On day E12 several axons were found to arborize in the SGFS. At this stage arbors appear to have small branches with less than 4 branching points. The extension of terminal arbors in the anterior/posterior (A/P) and in the dorsal/ventral (D/V) direction was determined for 50 axonal trees at days E13-14 and for 24 arbors at days E15-16. Few axonal terminals were investigated at day E18. The mean A/P extent of axonal terminal trees increases from 0.23 +/- 0.12 to 0.36 +/- 0.22 mm from E13-14 to E15-16 and seems to stay at this order of magnitude on E18. The mean D/V extent increases from 0.23 +/- 0.17 to 0.30 +/- 0.18 mm in the same embryonic period of development. The number of branching points calculated from the same number of axonal trees increases from 7.50 +/- 2.98 at E13-14 to 11.70 +/- 4.10 at E15-16. This number seems to increase further after day E16 achieving values of about 20 to 25 at E18. This was, however, not quantifiable by the technique used here and represents an approximate value estimated from 6 completely labeled terminal fields at E18. The data presented here suggest that the modeling of the final branching pattern in the chick retinotectal system takes place within a relatively short period of embryonic development. Prior to the beginning of terminal arborization two important events contribute to the formation of a retinotopic projection. One event is the change of the D/V position by a minority of axons lying ectopic in terms of retinotopy. Some axons turn at right angles and change their D/V position. The other event is the appearance of side branches along the A/P axis.

Outgrowth and directional specificity of fibers from embryonic retinal transplants in the chick optic tectum

Retinal pieces taken from known positions of 6-day chick embryos were vitally labeled with the fluorescent dye Rhodamine- B-isothiocyanate (RITC). They were then transferred onto the surfaces of optic tecta following early bilateral removal of the embryo's optic vesicles. One to 5 days after transplantation the tecta were fixed and transplants that issued fibers were examined on tectal wholemounts or were sectioned and viewed with a fluorescence microscope. Retinal fibers growing out from transplants on day E6 tecta showed a capacity for changing their initial outgrowth directions and for reorienting themselves towards their specific retinotopic projection area. Frequently, changes in growth direction appeared in a right-angled pattern. The capacity for turning was strongest for fibers of nasal retinal origin, less strong for fibers of temporal origin, and occurred rarely but unquantifiably in the case of fibers of ventral retinal origin. Fibers of all investigated retinal quadrants were found to reach their corresponding projection areas and to arborize there, that is, fibers of nasal retinal transplants in the posterior tectum, of temporal transplants in the anterior tectum, and of ventral transplants in the dorsal tectum. Furthermore, once in their target region, the fibers left the outer layer of the tectum and turned, again in right angles, to invade deeper layers. Capacity of fibers to turn towards their projection area was not observed for fibers issued from transplants placed on the tectum later than day E8. We suggest that there is a specific guidance of retinal axons on the tectum.

Topographic targeting errors in the retinocollicular projection and their elimination by selective ganglion cell death

In adult rats, as in other rodents, the retinocollicular projection is topographically organized in a very precise manner. Experiments involving the use of the retrogradely transported fluorescent dye fast blue as either a short- or long-term marker in neonatal rats indicate that the precision of this retinotopic projection does not arise ab initio, but rather is brought about by the preferential elimination of those ganglion cells whose axons project to topographically inappropriate regions of the colliculus. Such topographic targeting errors have been identified along both the rostrocaudal and mediolateral axes of the colliculus, and their elimination occurs during the period of naturally occurring ganglion cell death, which is completed by about postnatal day 10. When impulse activity in the retinal ganglion cell axons is blocked by repeated intraocular injections of the sodium channel-blocking agent tetrodotoxin (TTX) throughout the postnatal period of ganglion cell death, the preferential loss of the incorrectly projecting ganglion cells does not occur in the activity-blocked eye, although, as reported elsewhere, the overall loss of ganglion cells is comparable to that seen in normal animals. This supports the notion that the mechanism for selecting against incorrectly projecting ganglion cells is based on impulse activity among the competing ganglion cell axons. However, under activity-block conditions, the aberrantly projecting axons appear to retract from the caudal margin of the colliculus. The death of retinal ganglion cells during development thus seems to serve 2 purposes: It provides for the quantitative matching of the ganglion cell population to the needs of its central projection fields, and, at the same time, it serves to selectively eliminate those cells whose axons project to inappropriate targets or to inappropriate regions within the correct target fields.

Formation of retinotopic connections: selective stabilization by an activity-dependent mechanism.

During regeneration of the optic nerve in goldfish, the ingrowing retinal fibers successfully seek out their correct places in the overall retinotopic projection on the tectum. Chemospecific cell-surface interactions appear to be sufficient to organize only a crude retinotopic map on the tectum during regeneration. Precise retinotopic ordering appears to be achieved via an activity-dependent stabilization of appropriate synapses and is based upon the correlated activity of neighboring ganglion cells of the same receptive-field type in the retina. Four treatments have been found to block the sharpening process: (a) blocking the activity of the ganglion cells with intraocular tetrodotoxin (TTX), (b) rearing in total darkness, (c) correlating the activation of all ganglion cells via stroboscopic illumination and (d) blocking retinotectal synaptic transmission with alpha-bungarotoxin (alphaBTX). These experiments support a role for correlated visually driven activity in sharpening the diffuse projection and suggest that this correlated activity interacts within the postsynaptic cells, probably through the summation of excitatory postsynaptic potentials (EPSPs). Other experiments support the concept that effective synapses are stabilized: a local postsynaptic block of transmission causes a local disruption in the retinotectal map. The changes that occur during this disruption suggest that each arbor can move to maximize its synaptic efficacy. In development, initial retinotectal projections are often diffuse and may undergo a similar activity-dependent sharpening. Indirect retinotectal maps, as well as auditory maps, appear to be brought into register with the direct retinotopic projections by promoting the convergence of contacts with correlated activity. A similar mechanism may drive both the formation of ocular dominance patches in fish tectum and kitten visual cortex and the segregation of different receptive-field types in the lateral geniculate nucleus. Activity-dependent synaptic stabilization may therefore be a general mechanism whereby the diffuse projections of early development are brought to the precise, mature level of organization.

Rules of order in the retinotectal fascicles of goldfish

Individual fascicles of retinal axons were labeled in the goldfish tectum with horseradish peroxidase (HRP). The contralateral retina was later processed for HRP histochemistry to mark the cells that had axons in the fascicles. Labeled cells were found in a partial half anulus in ventral hemiretina, centered on the optic disk. The distance of the partial anulus from the disk depended on which tectal fascicle had been labeled; the more rostrocentral the fascicle, the smaller was the annular radius. The angular subtense of the partial anulus with respect to the disk depended on where (along its tectal course) the fascicle had been labeled; the more rostral the label site, the longer was the angular subtense. These results were interpreted in the context of retinotectal growth, and it was inferred that the axons followed two rules: (1) grow in along the edge of the tectum and (2) exit and terminate in order, axons from temporal retina first, nasal retina last. These rules would produce a retinotopic projection in peripheral tectum, but they require that some of the terminals already in place must shift as the tectum grows.

Target regulation of synaptic number in the compressed retinotectal projection of goldfish.

In order to determine the morphological consequences of the formation of a compressed retinotectal projection, the optic neuropil lamina (stratum fibrosum et griseum superficialis, SFGS) was examined in large goldfish 3 months to 4 years after ablation of the caudal half of the tectum both with crush of the optic nerve (HTX) without (HT). In semithin sections, the SFGS, as delineated with orthograde HRP labeling, shows a persistent hypertrophy of about 25% in HTX and HT groups. Comparison of ultrastructural stereological data with similar data on control and regenerated projections to intact tecta (Murray and Edwards, '82) indicated that this hypertrophy can be attributed largely to an increased number of axons and not to increases in terminal or dendritic compartments. A normal number of synaptic terminals per column through SFGS is conserved in HTX and HT groups. Planimetric analysis and observations using orthograde HRP labeling reveal no group differences in size and shape of terminal profiles. The same number of retinal ganglion cells project to a half-tectum as to an intact tectum, as indicated by estimates of ganglion cell number and of the minimum percentage of them which project to the tectum using retrograde HRP labeling. The results suggest that the regenerating and sprouting optic axons participating in the formation of a compressed retinotopic projection compete for a limited accommodation inthe SFGS and that this capacity to accept synaptic input becomes saturated at the control innervation density. The results are consistent with the formation of a smaller than normal number of terminals per optic axon, numerical estimates for which are given. If the percentage of terminals which are optic does not change, then the number of terminals per axon is reduced by about 40%.

Retinopic organization of the striate cortex (area 17) in the reeler mutant mouse

The retinotopic projection of the visual field onto the primary visual cortex (area 17) of the reeler mutant mouse was studied with extracellular unit recordings. The map is organized in a manner similar to that of the normal mouse, indicating that the absence of normal cortical lamination in the reeler does not prevent the thalamocortical afferents from establishing their normal retinotopic order.

Glaucoma Visual Field Analysis by Computed Profile of Nerve Fiber Function in Optic Disc Sectors

Automated perimetry has decreased the subjective aspects of data collection, but analysis has remained largely subjective. A microcomputer permits more objective analysis by regrouping and averaging data points in the threshold static visual field according to their retinotopic projection onto the optic disc rather than according to their eccentricity from the point of fixation. The applications of the technique include (1) following glaucomatous visual field loss, (2) differentiating glaucomatous from other forms of visual loss, and (3) studying the effects of aging on the visual field. Six formulas for data analysis are described, and their relative usefulness discussed. Percent loss or gain seemed to convey the most diagnostic information to the clinician. Percent of expected sensitivity was less than the decimal visual acuity when the diagnosis was glaucoma but greater when the diagnosis was cataract. In some cases this analytic method should provide information that could favorably affect patient management.

Chapter 4 Ordering of Retinotectal Connections: A Multivariate Operational Analysis

Publisher Summary This chapter attempts to analyze the retinotectal system in a more empirical and open-ended fashion than that generally associated with past models. The traditional view of the problem is considered to be erroneous—that is, that no single simple explanation can account for all the observations because the task is to integrate a number of interactive processes into a comprehensive understanding. Such an integrative approach offers an alternative to the current wave of numerical modeling and thus skirts thorny theoretical issues that are associated with simulations of poorly described complex systems. Most hypotheses about how optic fibers form a retinotopic projection onto tectum have relied on a single dominant process to generate order. These processes largely fall into one of three categories. In the oldest category are those hypotheses that assume that individual retinal fibers or tectal cells are intrinsically identical with each other. In the latter, fibers were found to grow to abnormal tectal positions following removal of part of retina or tectum. The third category of explanation arose as an answer to the plasticity results. In particular, these hypotheses address the capacity of optic fibers to preserve retinotopography when a whole retina “compresses” onto a surgically formed half tectum or when a half retina expands across a whole tectum.

Projections from visual areas of the middle suprasylvian sulcus onto the lateral posterior complex and adjacent thalamic nuclei in cat.

The distribution of corticothalamic projections from lateral suprasylvian areas AMLS, PMLS, ALLS, and PLLS was investigated with the autoradiographic method. Areas AMLS and PMLS were both found to project retinotopically upon the medial interlaminar nucleus and the lateral and pulvinar zones of the lateral posterior complex, as well as to the ventral lateral geniculate nucleus, intralaminar nuclei, and thalamic reticular complex. Retinotopic projections to the dorsal lateral geniculate nucleus were demonstrated from PMLS but not AMLS, and projections to zona incerta were demonstrated from AMLS but not PMLS. Areas PLLS and ALLS were both found to project retinotopically upon the interjacent zone of the lateral posterior complex, as well as to the intermediate and suprageniculate divisions of the posterior nuclear group, the magnocellular division of the medial geniculate complex, the thalamic reticular complex, and central lateral nucleus. Area ALLS was also found to project onto the dorsal division of the medial geniculate complex and lateral division of the posterior nuclear group. Differences between the four cortical areas in the pattern and density of their thalamic projections supports the parcellation of these areas as proposed by Palmer et al. ('78). The projection patterns of areas PMLS, AMLS, PLLS, and ALLS were found to respect the boundaries of the zones of the lateral posterior complex, which had been identified and defined previously (Updyke, '77), and the results thus support the hypothesis that these zones are the functional units of organization of visual traffic between the cat's extrastriate visual areas.

The visual claustrum of the cat. I. Structure and connections

The cat's dorsocaudal claustrum was studied in Golgi preparations, by electron microscopy, and by anterograde and retrograde tracer techniques. It receives a convergent retinotopic projection from several visual cortical ares, including areas 17, 18, 19, 21a and PMLS (posteromedial lateral suprasylvian area). The projection arises from spiny dendrite cells (pyramidal and fusiform) in the middle of cortical layer VI. As shown by a double label experiment, they form a separate population from those projecting to the lateral geniculate nucleus. There are also inputs from the lateral hypothalamus, from the nucleus centralis thalami, and probably from the locus coeruleus, but not from the sensory nuclei of the thalamus. Non-visual cortical areas do not project to the visual claustrum, but many of them are connected to other parts of the nucleus. For example, the splenial (cingulate) gyrus projects to a claustral zone just ventral to the visual area, and regions anterior to the visual area are connected with somatosensory and auditory cortex. The commonest cell type in the claustrum is a large spiny dendrite neuron whose axon leaves the nucleus after giving off local collaterals. Small spine-free cells, with beaded dendrites and a locally arborizing axon, are found also. Electron microscopy of the claustrum after ablation of the visual cortex showed degenerating type 1 axon terminals synapsing on spines and beaded dendrites, suggesting a direct cortical input to both cell types. The visual claustrum projects back to the visual cortex, to the same areas from which it receives an input. The return projection is predominantly ipsilateral, but there is, in addition, a small crossed projection. The claustrocortical axons terminate in all cortical layers but most heavily in layers IV and VI. The majority of the cells in the visual claustrum project to the cortex, and retinotopy is maintained throughout the entire corticoclaustral loop. No subcortical projections from the claustrum could be identified.

Projections from the superior colliculus and the neocortex to the pulvinar nucleus in Galago.

We have studied the projections from the superior colliculus and the neocortex to the pulvinar nucleus in Galago senegalensis by using the retrograde transport of horseradish peroxidase (HRP). Injections of various parts of the pulvinar complex, both the inferior and superior divisions, both the tectorecipient zone and the nontectorecipient zone as defined by Glendenning et. al. ('75), produce labeled cells in the lower tier of stratum griseum superficiale. The distribution of labeled cells in the superior colliculus varies with the locus of the injection, indicating a retinotopic projection system from the entire superior colliculus to all sectors of the pulvinar complex. These experiments also provide an opportunity to study the distribution and laminar origin of neurons giving rise to cortical descending projections. The entire visual cortex projects onto the pulvinar complex. The cells or origin can be divided into two populations--one located in layer V and the other in layer VI. In seven of the nine cases reported, the layer V population is restricted entirely or mainly to the striate area. In the two exceptional cases, the layer V population is located in the adjacent extrastriate cortex, areas 18 and 19. The difference in the layer of origin of the cortical descending fibers reflects a difference in the layer of termination of the reciprocal ascending projection. These findings identify the entire visual field as primary visual cortex. The importance of this conclusion is underscored by the fact that the visual field comprises as much as one-half of the whole neocortex.

Mapping the Representation of the Visual Field by Electrical Stimulation of Human Visual Cortex

Electrical stimulation of human visual cortex produces punctuate phosphenes in the visual field. This phenomenon, which is being explored as the basis for a visual prosthesis for the blind, also provides the first electrophysiological information about the retinocortical map in man. Stimulation of points clustered on the surface of the visual cortex produces phosphenes clustered in visual space. However, adjacent surface electrodes located on opposite sides of a sulcus can produce widely separated phosphenes, because the intervening cortex is buried and inaccessible to stimulation. Such electrodes can also produce multiple phosphenes by simultaneously stimulating both banks of the sulcus. Electrodes which are widely spaced on the brain can produce phosphenes close together in visual space providing they stimulate cortex corresponding to overlapping maps in areas 17 and 18. Analysis of the phosphene map indicates that successive stimulation of points further from the tip of the occipital pole produces phosphenes progressively more distant from the fixation point. Successive stimulation of points along the orthogonal dorsoventral dimension produces a progressive change in phosphene bearing. These results confirm the general view of cortical organization derived from field defect studies in man, and from anatomical and electrophysiological studies in monkeys, and provide a new tool for more detailed study of retinotopic projections in man.

Evidence from thymidine labeling for continuing growth of retina and tectum in juvenile goldfish

Tritiated thymidine was injected intraperitoneally into juvenile goldfish that were 3 to 6 cm in body length. After 6 h to 32 months these fish were then killed for autoradiography of retina and tectum. The autoradiographs indicated that despite the maturity of these goldfish both retina and tectum were still growing by the accretion of new cells at their margins. As was shown for Xenopus, new retinal cells were added around the entire retinal circumference, while new tectal cells were added principally around the posterior tectal margin and none to the anteriormost edge. However, goldfish of this size have a well-defined and functional retinotopic projection of retina onto tectum. This means that newly created ganglion cells of temporal retina, destined to send axons to anterior tectum, will find only old tectal cells at their target locus with which to connect. Presumably preexisting retinal terminals in the tectum must be shifted posteriorly to allow the new ganglion cells to find tectal synaptic sites.