Retinal Fibers Research Articles

Ocular dominance stripe formation by regenerated isogenic double temporal retina in Xenopus laevis

In lower vertebrates such as frogs and fish, long ocular dominance stripes with anterior-posterior (A-P) orientation can be produced by causing both eyes to innervate one optic tectum during the course of development. Similar experiments on adult animals usually produce patches rather than stripes. During development, new retinal fibers from the nasal retina segregate into appropriate stripes at the growing edge of the posterior (P) tectum while new temporal fibers segregate at the non-growing anterior (A) tectal edge. Fiber segregation into long A-P oriented stripes might depend upon a template produced by new nasal fibers initiating stripe orientation in the vicinity of new tectal cells; new nasal fibers would orient to the nascent (posterior) edge of the template while temporal fibers would orient to the anterior (non-growing) end of the template. To test the dependence of stripe formation on the matching of nascent retinal cells with nascent tectal cells, we compared stripe orientation in animals with isogenic double nasal innervation and isogenic double temporal innervation of the tectum. In double nasal innervation, the oldest retinal cells innervate the anterior tectum; new fibers from the entire retinal periphery always innervate the newest tectal cells at the posterior tectum. Stripes are oriented A-P, consistent with a maturation front model. In contrast, the oldest retinal cells innervate the newest (posterior) tectal cells in double temporal innervation of the tectum; the growing retinal periphery innervates the non-growing anterior tectum. Stripes are also oriented A-P, indicating that the production of long stripes does not depend upon maturation front matching of nascent retinal fibers and nascent tectal cells.

Effect of optic nerve lesions and intraocular colchicine on cell proliferation in the germinal zone of the optic tectum and in the torus longitudinalis in the goldfish

Postembryonic development of the optic tectum occurs in part through proliferation of cells in the germinal zone located at the caudal edges of each lobe. Autoradiography experiments by others have shown that [ 3H]thymidine labeling in the germinal zone is decreased following optic nerve crush or enucleation and restored above normal levels during optic nerve regeneration. The present autoradiography experiments examined the relationship between retinal innervation and the rate mitotic activity in the tectum germinal zone and in the torus longitudinalis. The fish received optic nerve crush to temporarily deafferent the tectum, enucleation for permanent deafferentiation, or an intraocular injection of 0.01–1.0 μg of colchicine to reversibly inhibit axonal transport in the optic nerve. Thymidine labeling in the tectum germinal zone showed that nerve crush resulted in decreased mitotic activity in most fish within 6 days followed by recovery by 21 days; enucleation decreased mitotic activity more uniformly and for more than 42 days with recovery by 84 days postaxotomy; colchicine produced a dose-dependent inhibition of mitotic activity which was reversed by 42 days postinjection. Axonal transport was restored by 42 days postinjection. In the torus longitudinalis, nerve crush produced a brief increase in mitotic activity followed by a return to a normal; enucleation and colchicine resulted in a lasting decrease in mitotic activity and atrophy indicating a loss of cells or neuropil. The data are consistent with the proposal that cell proliferation in the tectum germinal zone is stimulated by the accretion of fibers from developing retinal ganglion cells. Axonal transport of cellular materials in mature retinal fibers may also be involved. The results further suggest that the torus longitudinalis undergoes postembryonic development apace the optic tectum, and that its growth, like that of the tectum, is stimulated by the eye.

Differentiation of avian retinotectal projection

The topographic relationship between the retina and tectum is strict. Retinal fibers, however, overpass the target and distribute wider mediolaterally when they first enter the tectum. Retinal fibers find their target by sending collateral branches. Tetrodotoxin (TTX) treatment shows that neuronal activity plays a role in refinement of the retinal fibers. The rostrocaudal axis of the tectum anlage was rotated 180 degrees at about the 10-somite stage. The results showed that the polarity of the transplants was regulated and adjusted to that of the host embryo. It is suggested that the rostrocaudal polarity of the tectum anlage is not determined at about the 10-somite stage.

Ipsilateral Retinofugal Projections in a Percomorph Bony Fish: Their Experimental Induction, Specificity and Maintenance; pp. 286–292

Adult bony fish possess only a small ipsilateral retinofugal projection, if any. Experimental manipulation, such as unilateral enucleation, can lead to an enhancement of this projection. We examined the patterns of, as well as the conditions for the development and maintenance of an enhanced ipsilateral retinofugal projection (EIRP) after nerve crush, after enucleation, and after various combinations of both types of surgery in juvenile and adult <i>Haplochromis burtoni </i>(Cichlidae). Retinal projections were labeled either unilaterally with horseradish perixodase, or with the lipophilic fluorescent dye DiI in aldehyde-fixed animals, or bilaterally with differently colored fluorescent dextran amines. Unilateral nerve crush always leads to the regeneration of retinofugal fibers to the contralateral tectum but spares some contralateral diencephalic nuclei. In addition, unilateral or bilateral nerve crush in many cases, and unilateral enucleation in some cases, leads to the development of an EIRP to the ipsilateral diencephalon and tectum. This EIRP persists (4 months and longer postoperatively) in only 10% of the unilaterally enucleated animals, in none of the animals subjected to unilateral nerve crush and in 79% of the animals subjected to bilateral nerve crush. All unilaterally enucleated animals in which the remaining, contralateral optic nerve was crushed develop and maintain an EIRP. These data suggest that nerve crush alone is sufficient to cause regenerating fibers to project, at least transiently, to the ipsilateral side of the brain. When the normal contralateral projection is either absent or in the process of regeneration, an EIRP can be maintained. In the latter case, alternate bands or patches of ipsi- and contralateral fibers in the tectum may result. Ipsilateral fibers follow unusual pathways by recrossing at the rostral diencephalon. Likewise, regenerating contralateral retinal fibers grow differently in this area; here, where the optic-nerve projection is reorganized into the optic tract, many regenerating fibers are deflected to the ipsilateral side of the brain. Despite atypical routes taken by some fibers, the EIRP nevertheless ends only in specific retinorecipient areas. An EIRP develops independently of the age of the animal, independently of the time lapse between enucleation and nerve lesion, and independently of persisting debris. However, in animals receiving an optic nerve lesion a long time after unilateral enucleation, the size of the EIRP and its tectal extent are reduced compared to that in animals enucleated around the same time as receiving the crush of the contralateral optic nerve.

Retinofugal and Retinopetal Projections in the Pacific Hagfish, &lt;i&gt;Eptatretus stouti &lt;/i&gt;(Myxinoidea) (Part 1 of 2)

The retinofugal and retinopetal connections of the Pacific hagfish were determined using the fluorescent compound DiI as an in vitro tracer. The retinofugal connections were found to be bilateral and to reach preoptic, thalamic and pretectal, as well as tectal, targets. No distinct basal optic root was found. A retinopetal projection in hagfishes is described here for the first time. It originates from two cells groups in the rostral mesencephalic tegmentum. These retinal connections in hagfishes are compared to the organization of the visual system in the second Recent group of jawless fishes, the lampreys. Both visual systems are similar in the number and location of the targets of retinal fibers. Furthermore, there is a striking similarity in the retinopetal systems. Major differences are found in the organization of the optic tract. These observations allow the identification of some cell groups not previously recognized in myxinoid brains or interpreted differently. Finally, the findings are discussed in relation to visually guided behavior in hagfishes.

Ipsilateral Retinofugal Projections in a Percomorph Bony Fish: Their Experimental Induction, Specificity and Maintenance; pp. 271–278

Adult bony fish possess only a small ipsilateral retinofugal projection, if any. Experimental manipulation, such as unilateral enucleation, can lead to an enhancement of this projection. We examined the patterns of, as well as the conditions for the development and maintenance of an enhanced ipsilateral retinofugal projection (EIRP) after nerve crush, after enucleation, and after various combinations of both types of surgery in juvenile and adult Haplochromis burtoni (Cichlidae). Retinal projections were labeled either unilaterally with horseradish perixodase, or with the lipophilic fluorescent dye DiI in aldehyde-fixed animals, or bilaterally with differently colored fluorescent dextran amines. Unilateral nerve crush always leads to the regeneration of retinofugal fibers to the contralateral tectum but spares some contralateral diencephalic nuclei. In addition, unilateral or bilateral nerve crush in many cases, and unilateral enucleation in some cases, leads to the development of an EIRP to the ipsilateral diencephalon and tectum. This EIRP persists (4 months and longer postoperatively) in only 10% of the unilaterally enucleated animals, in none of the animals subjected to unilateral nerve crush and in 79% of the animals subjected to bilateral nerve crush. All unilaterally enucleated animals in which the remaining, contralateral optic nerve was crushed develop and maintain an EIRP. These data suggest that nerve crush alone is sufficient to cause regenerating fibers to project, at least transiently, to the ipsilateral side of the brain. When the normal contralateral projection is either absent or in the process of regeneration, an EIRP can be maintained. In the latter case, alternate bands or patches of ipsi- and contralateral fibers in the tectum may result. Ipsilateral fibers follow unusual pathways by recrossing at the rostral diencephalon. Likewise, regenerating contralateral retinal fibers grow differently in this area; here, where the optic-nerve projection is reorganized into the optic tract, many regenerating fibers are deflected to the ipsilateral side of the brain. Despite atypical routes taken by some fibers, the EIRP nevertheless ends only in specific retinorecipient areas. An EIRP develops independently of the age of the animal, independently of the time lapse between enucleation and nerve lesion, and independently of persisting debris. However, in animals receiving an optic nerve lesion a long time after unilateral enucleation, the size of the EIRP and its tectal extent are reduced compared to that in animals enucleated around the same time as receiving the crush of the contralateral optic nerve.

Ipsilateral Retinofugal Projections in a Percomorph Bony Fish: Their Experimental Induction, Specificity and Maintenance; pp. 293–299

Adult bony fish possess only a small ipsilateral retinofugal projection, if any. Experimental manipulation, such as unilateral enucleation, can lead to an enhancement of this projection. We examined the patterns of, as well as the conditions for the development and maintenance of an enhanced ipsilateral retinofugal projection (EIRP) after nerve crush, after enucleation, and after various combinations of both types of surgery in juvenile and adult <i>Haplochromis burtoni </i>(Cichlidae). Retinal projections were labeled either unilaterally with horseradish perixodase, or with the lipophilic fluorescent dye DiI in aldehyde-fixed animals, or bilaterally with differently colored fluorescent dextran amines. Unilateral nerve crush always leads to the regeneration of retinofugal fibers to the contralateral tectum but spares some contralateral diencephalic nuclei. In addition, unilateral or bilateral nerve crush in many cases, and unilateral enucleation in some cases, leads to the development of an EIRP to the ipsilateral diencephalon and tectum. This EIRP persists (4 months and longer postoperatively) in only 10% of the unilaterally enucleated animals, in none of the animals subjected to unilateral nerve crush and in 79% of the animals subjected to bilateral nerve crush. All unilaterally enucleated animals in which the remaining, contralateral optic nerve was crushed develop and maintain an EIRP. These data suggest that nerve crush alone is sufficient to cause regenerating fibers to project, at least transiently, to the ipsilateral side of the brain. When the normal contralateral projection is either absent or in the process of regeneration, an EIRP can be maintained. In the latter case, alternate bands or patches of ipsi- and contralateral fibers in the tectum may result. Ipsilateral fibers follow unusual pathways by recrossing at the rostral diencephalon. Likewise, regenerating contralateral retinal fibers grow differently in this area; here, where the optic-nerve projection is reorganized into the optic tract, many regenerating fibers are deflected to the ipsilateral side of the brain. Despite atypical routes taken by some fibers, the EIRP nevertheless ends only in specific retinorecipient areas. An EIRP develops independently of the age of the animal, independently of the time lapse between enucleation and nerve lesion, and independently of persisting debris. However, in animals receiving an optic nerve lesion a long time after unilateral enucleation, the size of the EIRP and its tectal extent are reduced compared to that in animals enucleated around the same time as receiving the crush of the contralateral optic nerve.

Ipsilateral Retinofugal Projections in a Percomorph Bony Fish: Their Experimental Induction, Specificity and Maintenance; pp. 279–285

Adult bony fish possess only a small ipsilateral retinofugal projection, if any. Experimental manipulation, such as unilateral enucleation, can lead to an enhancement of this projection. We examined the patterns of, as well as the conditions for the development and maintenance of an enhanced ipsilateral retinofugal projection (EIRP) after nerve crush, after enucleation, and after various combinations of both types of surgery in juvenile and adult <i>Haplochromis burtoni </i>(Cichlidae). Retinal projections were labeled either unilaterally with horseradish perixodase, or with the lipophilic fluorescent dye DiI in aldehyde-fixed animals, or bilaterally with differently colored fluorescent dextran amines. Unilateral nerve crush always leads to the regeneration of retinofugal fibers to the contralateral tectum but spares some contralateral diencephalic nuclei. In addition, unilateral or bilateral nerve crush in many cases, and unilateral enucleation in some cases, leads to the development of an EIRP to the ipsilateral diencephalon and tectum. This EIRP persists (4 months and longer postoperatively) in only 10% of the unilaterally enucleated animals, in none of the animals subjected to unilateral nerve crush and in 79% of the animals subjected to bilateral nerve crush. All unilaterally enucleated animals in which the remaining, contralateral optic nerve was crushed develop and maintain an EIRP. These data suggest that nerve crush alone is sufficient to cause regenerating fibers to project, at least transiently, to the ipsilateral side of the brain. When the normal contralateral projection is either absent or in the process of regeneration, an EIRP can be maintained. In the latter case, alternate bands or patches of ipsi- and contralateral fibers in the tectum may result. Ipsilateral fibers follow unusual pathways by recrossing at the rostral diencephalon. Likewise, regenerating contralateral retinal fibers grow differently in this area; here, where the optic-nerve projection is reorganized into the optic tract, many regenerating fibers are deflected to the ipsilateral side of the brain. Despite atypical routes taken by some fibers, the EIRP nevertheless ends only in specific retinorecipient areas. An EIRP develops independently of the age of the animal, independently of the time lapse between enucleation and nerve lesion, and independently of persisting debris. However, in animals receiving an optic nerve lesion a long time after unilateral enucleation, the size of the EIRP and its tectal extent are reduced compared to that in animals enucleated around the same time as receiving the crush of the contralateral optic nerve.

Retinofugal and Retinopetal Projections in the Pacific Hagfish, &lt;i&gt;Eptatretus stouti &lt;/i&gt;(Myxinoidea) (Part 2 of 2)

The retinofugal and retinopetal connections of the Pacific hagfish were determined using the fluorescent compound DiI as an <i>in vitro</i> tracer. The retinofugal connections were found to be bilateral and to reach preoptic;, thalamic and pretectal, as well as tectal, targets. No distinct basal optic root was found. A retinopetal projection in hagfishes is described here for the first time. It originates from two cell groups in the rostral mesencephalic tegmentum. These retinal connections in hagfishes are compared to the organization of the visual system in the second Recent group of jawless fishes, the lampreys. Both visual systems are similar in the number and location of the targets of retinal fibers. Furthermore, there is a striking similarity in the retinopetal systems. Major differences are found in the organization of the optic tract. These observations allow the identification of some cell groups not previously recognized in myxinoid brains or interpreted differently. Finally, the findings are discussed in relation to visually guided behavior in hagfishes.

Photically responsive neurons in the hypothalamus of a diurnal ground squirrel

The suprachiasmatic nuclei (SCN) function as a circadian pacemaker. Entrainment to the external light-dark cycle is mediated by the retina which gives rise to both direct and indirect projections to the SCN. The hypothalamic targets of the retinohypothalamic tract (RHT) were investigated in thirteen-lined ground squirrels ( Spermophilus tridecemlineatus) following WGA-HRP injections. The results indicate that retinal fibers project to the entire SCN. Extracellular single-unit activity was recorded in and near the SCN of thiopental sodium anesthetized squirrels while the eyes were photically stimulated. A small population of hypothalamic cells were responsive to retinal illumination. About half of these cells were activated by light while the others were light-suppressed. The majority of these cells responded in a sustained way to light pulses. Light intensities of at least 1000 lux appeared necessary to induce a sustained response to light. No differences in light responsiveness were observed between visual cells inside and outside the SCN. The visual properties of SCN cells have previously been investigated in hamsters and rats, both nocturnal species. Hypothalamic cells in all 3 species were similar in that they showed predominantly sustained responses to retinal illumination. The diurnal squirrel differed from the other two species in that there was a higher proportion of photically suppressed cells in the squirrel, and in that higher light intensities were required to stimulate photically responsive neurons.

Relationship between isthmotectal fibers and other tectopetal systems in the leopard frog.

We studied the relationship of isthmotectal input to other tectal afferent fiber systems in three ways. 1) Using horseradish peroxidase (HRP) histochemistry, we determined the nonretinal inputs to the superficial tectum. In different sets of animals we a) applied HRP to the tectal surface; b) inserted HRP crystals into the tectum; c) injected small volumes of HRP solutions into the superficial tectum. N. isthmi accounts for more than 65% of the nonretinal extrinsic input in the superficial tectal layers. One set of fibers from the contralateral n. isthmi projects to the most superficial layer. Fibers from posterior thalamus and tegmentum project to both superficial and deeper layers in the tectum, but not to the most superficial layer. The ipsilaterally projecting isthmotectal fibers terminate in the deeper superficial layers. 2) We investigated the relationship between retinofugal and contralaterally projecting isthmotectal pathways. We orthogradely labelled n. isthmi fibers by unilateral HRP injections into n. isthmi, and we also labelled retinal fibers by injecting tritiated l-proline into both eyes. In such animals contralaterally projecting isthmotectal fibers cross in the dorsal posterior region of the optic chiasm. From the chiasm to the tectum isthmotectal fibers and retinofugal fibers are admixed. 3) We determined whether other fiber systems cross with contralaterally projecting isthmotectal fibers. We cut the posterior part of the optic chiasm and applied HRP crystals to the cut. Only n. isthmi and retina are retrogradely labelled.

Prenatal development of retinocollicular projections in the rabbit: an HRP study.

The prenatal development of the rabbit's retinal projections to the superior colliculus (SC) was studied by using anterograde transport of horseradish peroxidase injected intraocularly. Fetuses aged embryonic day 21 (E21) to E29 and an adult rabbit were examined. Gestation in the rabbit is 30-31 days. On E21 contralaterally projecting retinal fibers invade across the entire SC. Their distribution is initially diffuse within the superficial laminae, but by E29 they have a distinct stratified appearance. Ipsilaterally projecting retinal fibers invade the rostral half of the SC on E21. By E23 they cover the entire SC and overlap the contralateral fibers both tangentially and radially. The ipsilateral fibers for the most part are sparsely distributed, but they form a dense focal distribution in the rostrolateral quarter of the SC. This focus straddles the stratum griseum superficiale/stratum opticum (SGS/SO) border. On E25 the ipsilateral fibers maintain their widespread distribution and focal rostrolateral concentration. By E27 they are excluded almost entirely from the caudal half of the SC and are reduced in density in the rostromedial quarter of the nucleus. On E29 the ipsilateral terminal field forms distinct patches and bands that are restricted to the rostrolateral quarter of the SC and are confined to the SGS/SO border. Thus, a few days before birth the pattern and location of the ipsilateral retinocollicular projection resemble those seen in the adult. The early widespread distribution of the ipsilaterally projecting retinal fibers to the SC and their eventual restriction in the fetal rabbit are consistent with the development of this projection in other mammalian orders.

Retinogeniculate projection fibers in the monkey optic nerve: A demonstration of the fiber pathways by retrograde axonal transport of WGA‐HRP

Seven Japanese monkeys (Macaca fuscata) were used to investigate the fiber pathways of the optic nerve. Optic nerve fibers and retinal ganglion cells were retrogradely labeled by iontophoretic injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into electrophysiologically defined positions of the lateral geniculate nucleus (LGN). By gross anatomical observation, the optic nerve usually had one distinct bend, which flexed dorsally 3-4 mm from the eyeball, and occasionally another ventrally directed bend was found just behind the eyeball. In the optic nerve head, fibers from the various retinal areas were arranged in a wedge according to the fiber trajectory on the retinal surface. For about a 3 mm distance from the disc, fibers rapidly spread out radially. Subsequently, rather than scattering dorsoventrally, they progressed to the chiasm with a gradual increase in the degree of mediolateral (nasotemporal) scatter. The degree of the scatter was different depending on the retinal site from which the axons originated. Fibers from the peripheral retina spread out widely for a few millimeters behind the eyeball. Thereafter the scatter was rather limited until the chiasm. On the other hand, the scatter of fibers from the foveal and parafoveal areas progressed gradually through the nerve. The present study also suggests that the difference in scatter depends on the types of cells of origin. Fibers from large ganglion cells displayed more extensive scatter than fibers from medium-sized cells. In spite of the extensive scatter of fibers, two clear segregations were found; one was a dorsoventral segregation, which was displayed by both central and peripheral retinal fibers, and the other was a center-peripheral segregation in which the fibers from the nasal central (papillomacular) retina were located almost exclusively in the central part of the optic nerve surrounded by peripheral retinal fibers. However, the temporal central retinal fibers were located in the lateral periphery of the nerve, and they overlapped significantly with fibers from the temporal peripheral retina. Furthermore, a broad intermingling was found between nasal and temporal peripheral retinal fibers owing to their mediolateral scatter. Thus, the present findings based on more precise anatomical techniques indicate that the classical notion of the retinal quadrant topography in the monkey optic nerve probably is suspect. In addition, the "rotation" of the fiber arrangement was not demonstrated.

Cross-species recognition of tectal cues by retinal fibers in vitro

The retinae of vertebrates project in a topographic manner to several visual centers of the brain. The formation of these projections could depend on the existence of position-specific properties of retinal and target cells. In this study, we have tested the in vitro growth of mouse retinal fibers on membranes derived from various regions of the embryonic superior colliculus, a main target of the retina in this species. Fibers had the choice of elongating on membranes taken from either the anterior or the posterior half of the superior colliculus. Fibers from temporal areas of the retina prefer to elongate on anterior collicular membranes, while fibers from nasal areas do not show a preference. These phenomena are observed with membranes from embryonic (E15-E18) or young postnatal mice. In interspecies cultures where mouse retinal fibers had to grow on chick tectal membranes, or vice versa, the same preference for anterior tectal or collicular membranes in growth of temporal retinal fibers is observed, suggesting some similarities in the cues used in both species.

Retinofugal projections in the rufous horseshoe bat, Rhinolophus rouxi.

The retinal projections in the horseshoe bat were studied with anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Retinal fibers clearly terminate bilaterally in the lateral geniculate nuclei, superior colliculus, pretectal area, and nucleus of the optic tract. The suprachiasmatic nucleus and the lateral terminal nucleus of the accessory optic tract receive extremely weak, through bilateral retinal input. No projections to medial and dorsal accessory optic nuclei were found. There was a limited retinal projection to the ipsilateral dorsal geniculate nucleus. The focus of the ipsilateral projection corresponded to a less densely labeled region on the contralateral side. In this study an ipsilateral retinal projection to the anterior superior colliculus is documented for the first time in a Microchiropteran bat. In the contralateral superior colliculus retinal fibers terminate in a patch-like pattern at caudal levels.

Die retinale Nervenfaserschicht in Normal-und Glaukomaugen - Teil 1: Semiquantitative Daten von 398 Glaukomaugen

Atrophy of the optic nerve is associated with changes of the retinal fiber layer (RNFL). Using red-free photographs the authors examined the RNFL of 398 eyes with chronic primary open-angle glaucoma and compared it with the RNFL of 234 normal eyes. The glaucoma group was divided into five stages and the fundus into four sectors. Differences between the normal and glaucoma eyes were: (1) The sequence of the sectors, with regard to the best visibility of the retinal nerve fiber bundles, was changed. In the normal eyes the nerve fiber bundles were most often best visible in the inferior temporal sector, followed by the superior temporal sector, the temporal horizontal area and finally the nasal region. In the glaucoma group the nerve fiber bundles were significantly more often best detectable in the superior temporal sector and the temporal horizontal area. (2) The degree of visibility of the retinal nerve fibers decreased significantly with increasing glaucoma stage. (3) Localized defects were seen in 15% of the eyes with glaucoma and none of the normal eyes. The specificity of this qualitative parameter was, therefore, 100%. The defects were found most often in the superior and inferior temporal regions. These differences between normal and glaucomatous eyes were also significant for the first glaucoma stage of this study. The localization of the foveola below the optic disk center (0.53 +/- 0.34 mm in the glaucoma group and 0.55 +/- 0.29 mm in the normal eyes) was not significantly different.

Effects of intraocular tetrodotoxin on the development of the retinocollicular pathway in the Syrian hamster.

The developing uncrossed retinocollicular projection in the Syrian hamster undergoes a characteristic set of changes during the first 2 postnatal weeks. The retinal fibres, which initially project across the whole superior colliculus, withdraw from the caudal part and their terminals become clustered into deep, discrete clumps rostrally. Coincident with these afferent changes, there is substantial retinal ganglion cell death. To examine whether neuronal activity plays a role in these changes, we made daily injections of the sodium channel blocker tetrodotoxin (TTX) into one or both eyes from postnatal day 2 or 4 up to day 12. Following TTX treatment, the uncrossed terminals retracted on schedule from the caudal and superficial parts of the superior colliculus and came to lie, as normal, in the deep layers rostrally. Within the rostral superior colliculus, however, the uncrossed terminals from TTX-injected eyes lost their characteristic patchy distribution and were arranged diffusely. When only one eye received TTX injections, this inhibiting effect on terminal segregation was seen only in the projections from the TTX-treated eye. The effect of TTX treatment on terminal segregation was much less severe than that of unilateral enucleation, after which uncrossed terminals persis throughout the entire superior colliculus. TTX injections appeared to have little effect on overall ganglion cell death since the total number of ganglion cells in the crossed projection from TTX-treated eyes was similar to that in normal eyes. However, the relative distribution of uncrossed cells in temporal and nasal retina was altered. In eyes that received TTX injections, the proportion of uncrossed cells in nasal retina was about 1.6 times that in normal animals and was close to the proportion seen in unilaterally enucleated animals. This increase in the treated eye occurred whether one or both eyes were injected with TTX. We conclude that neuronal activity plays a role in the segregation of uncrossed terminals into discrete clumps in rostral colliculus and in the preferential elimination of uncrossed cells from the nasal retina. The inactive uncrossed projections from TTX-treated eyes showed the greatest degree of disruption. The extent of the disruption was similar whether the crossed input from the other eye was active or inactive. This suggests that the activity-drive interactions between ganglion cells within one eye are more significant than those between the two eyes in shaping the final form of the uncrossed retinocollicular projection.

Spatial arrangement of radial glia and ingrowing retinal axons in the chick optic tectum during development

Neuroanatomical tracing of retinal axons and axonal terminals with the fluorescent dye, Dil, was combined with immunohistochemical characterization of radial glial cells in the developing chick retinotectal system. Emphasis was placed on the mode of the tectal innervation by individual retinal axons and on the distribution and fate of the tectal radial glial cells and their spatial relation to retinal axons. It was obvious from fluorescent images obtained from anterogradely filled axons that these axons deserted the superficial stratum opticum (SO) to penetrate the stratum griseum et fibrosum superficiale (SGFS) by making right-angled turns within the SO. Frequently, axons which had invaded the SGFS were bifurcated and had a superficial branch which remained within the SO. Terminal axonal arborization occurred at various depths within the SGFS. Characterization of the tectal glial cells and their radial fibers by means of the anti-filament antibody, R5, and post-mortem staining with the fluorescent dye, Dil, revealed the following. (a) At least from day E8 to P1, tectal glial fibers traversed all tectal layers from the periventricular location of their somata to the superficial interface between SO and pia mater. In this interface they enlarged and formed characteristic endfeet. (b) Glial endfeet covered the whole tectal surface. They showed at early ages anterior-posterior differences having a higher density in the posterior tectum. These differences disappeared at embryonic day E13. (c) After innervation, glial endfeet of the anterior tectal third were arranged in rows parallel to the retinal fibers within the SO. This arrangement was not observed in eyeless embryos. (d) Radial glial fibers could be stained with R5 from day E8 to late embryonic stages throughout their entire length. (e) At the first posthatching days, only the segments of the radial glial fibers restricted to the thickness of the SO were R5-positive, although the fibers still traversed throughout the depth of the tectum. The results are discussed in context to the genesis of the retinotectal projection.

Transformations of the retinal topography along the visual pathway of the chicken.

It is still unclear how the retinotectal map of the chick is formed during development. In particular, it is not yet known whether or not the organization of fibres plays a role in the formation of this map. In order to contribute to the solution of this problem, we analysed the representation of the retinal topography at closely spaced intervals along the fibre pathway. We injected HRP into various sites of the tectal surface and traced the labelled fibre bundles back to the retina. The retinal topography was reconstructed at ten different levels, i.e. in the retina, the optic nerve head, the middle of the optic nerve, the chiasm (three levels), the optic tract (three levels), and the optic tectum. We obtained the following results: (1) The labelled fibre bundles as well as the fields of labelled retinal ganglion cells were always well delimited and coherent. (2) The reconstructions show that transformations of the retinal topography occur in the fibre pathway. The first and most important transformation is found in the optic nerve head where the retinal image is mirrored across an axis extending from dorsotemporal to ventronasal retina. In addition, the retinal representation is split in its temporal periphery. Thus, central and centrotemporal fibres are no longer in the centre of the image but close to the dorsal border of the nerve. Peripheral fibres are found along the medial, ventral and lateral circumference of the nerve. In the optic tract a second transformation occurs. The retinal topography is rotated clockwise by about 90 degrees and flattened to a band. The flattening is accompanied by a segregation of fibre bundles so that eventually central and centrotemporal retinal fibres are located centrally, ventral fibres dorsally and dorsal retinal fibres ventrally in the tract. By these two transformations an organization of fibres is produced in the optic tract which can be projected onto the tectal surface without major changes given that dorsal and ventral fibres remain in their relative positions, and that deep lying fibres project to the rostral and central tectum, superficial fibres to the caudal tectum. The transformations which we have observed follow specific rules and thus maintain order in the pathway although retinotopy is lost. In conjunction with our earlier studies on the development of the retinotectal system we conclude that fibres are laid down in a chronotopic order. The transformations take place under particular structural constraints.(ABSTRACT TRUNCATED AT 400 WORDS)

Loss of entrainment and anatomical plasticity after lesions of the hamster retinohypothalamic tract

The suprachiasmatic nuclei receive photic input information directly through a retinohypothalamic tract (RHT) and indirectly through a projection from the intergeniculate leaflet of the lateral geniculate complex, the geniculohypothalamic tract (GHT). Prior work has established that the RHT is sufficient for entrainment, but has not shown whether it is necessary because it has not been possible to transect that pathway. The present study addresses this problem by employing knife cuts to sever the RHT in male hamsters. Three knife cut procedures were used and one of these succeeded in separating the SCN from the optic chiasm in 8 animals with limited damage to the chiasm and the SCN. The effectiveness of the RHT lesion was confirmed by cholera toxin-HRP histochemistry which demonstrated that the knife cuts eliminate the normal retinal innervation of the SCN while sparing projections to thalamic and tectal visual centers. In a light-dark cycle, the lesioned animals exhibit free-running rhythms indicating that the RHT is necessary for entrainment. A surprising observation is the presence of extensive axonal sprouting of retinal fibers in brains of animals with RHT lesions. The newly-formed axons grow extensively into the SCN, anterior hypothalamus and basal forebrain, but form anomalous axonal plexuses which have no evident function.