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R W Guillery

Publications and source records attributed to R W Guillery.

At least 19 recordsLinked to original sources

Time of ganglion cell genesis in relation to the chiasmatic pathway choice of retinofugal axons.

The time of generation of retinal ganglion cells in fetal cats has been related to the course taken later by their axons in the optic chiasm. The ganglion cells were labelled with tritiated thymidine either on embryonic day (E) 26 or on E-30. When the cats were mature, ganglion cells were retrogradely labelled with horseradish peroxidase injected into one optic tract. The distribution of double-labelled cells showed that cells in the temporal retina generated on E-26 all have axons that take an uncrossed course in the chiasm, whereas, of the cells generated on E-30 in the temporal retina, some take a crossed course and others take an uncrossed course. The uncrossed axons of the E-26 cohort come from cells having a central distribution on the retina. For the E-30 cohort, the uncrossed axons come from cells having a relatively peripheral distribution, whereas the crossed axons come from more central cells. The present results suggest that the mechanism which serves to direct temporal retinal axons into the ipsilateral optic tract weakens as development proceeds. In principle, the change may occur in either a chiasmatic signal, read by temporal but not nasal optic axons, or in a retinal label, carried by temporal but not nasal cells and their processes. Since temporal retinal cells born concurrently at different places can project to opposite optic tracts, a retinal signal that deteriorates with time in a centroperipheral fashion is favored by the present results.

Animals

Observations on the early development of the optic nerve and tract of the mouse.

The early development of the retinofugal pathway of mice has been studied by light and electron microscopic methods in order to define the spatial distribution and the structure of the growth cones as they advance from the eye to the brain. We have studied the relationships of the growth cones to each other, to the glia and, in the older individuals, to the nerve fibers that are already terminating in the brain. We have looked at the rate of advance of the growth cones and have paid particular attention to the changing relationships of the growth cones as they approach the optic chiasm. We have also looked to see whether, at early stages, it is possible to recognise any characteristic features distinguishing the fibers destined to be the thickest in the adult, which come from ganglion cells that are generated among the earliest ganglion cells. In transverse sections through the optic stalk about 50-100 microns behind the eye, the first bundles of fibers are seen on embryonic day 12.5 (E12.5) as a mixture of thin (less than 0.5 micron) axons, thicker growth cones, and fine filopodial and foliopodial extensions. During the next two days, as these bundles in the intraorbital nerve increase in size and number, growth cones can be seen in all of the bundles and in all parts of the bundles. They show only a slight preference for one part of the nerve relative to another, and our material provides no evidence for the view that axons are particularly inclined to follow pre-existing bundles. The structure of the pathway changes significantly as it is traced towards the chiasm, and no section or small stretch of sections can be regarded as representative of the nerve as a whole. As the fibers approach the optic chiasm the growth cones come to lie predominantly close to the pial surface, with the deeper regions occupied almost entirely by fine axons. The change occurs in a region where the glial environment also changes, and where a characteristic neural tube-like organization first becomes recognizable. Here the glial cells lie in a periventricular position and send slender radial processes out towards the subpial surface. The newly invading axons in the early optic nerve taper from a broad growth cone back to an extremely slender axon, less than 0.5 micron in diameter. The tapered region is of the order of 100-300 microns in length and advances through the nerve at approximately 60 microns per hour.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Position of axons in the cat's optic tract in relation to their retinal origin and chiasmatic pathway.

The positions of the crossed and uncrossed optic axons of distinct diameter classes has been examined in the optic tract of the adult cat. In addition, the retinal origin of axons occupying different positions within the tract has been studied. Since the position of a fibre within the optic tract reflects its time of arrival during development, we have used axonal position as an indicator of age and have related this to the chiasmatic pathway choice of the axons. Cats were either monocularly enucleated, to reveal the position and diameter of surviving crossed and uncrossed optic axons in semithin and thin sections, or implants of horseradish peroxidase (HRP) were placed so as to retrogradely label the ganglion cells giving rise to axons within the deep (early arriving), or superficial (later arriving) parts of the tract selectively. This was accomplished by either 1) surgically implanting HRP into the superficial portion of the optic tract, via a transbuccal approach, or 2) making such a transbuccal transection of the superficial fibres, followed by intracerebral injections of HRP to retrogradely label the surviving, deeper, optic axons from their target nuclei. The deep parts of the optic tract contain fine and medium, crossed and uncrossed axons arising from mainly medium sized cells in the contralateral nasal and the ipsilateral temporal retina; there is a clear line of decussation. In contrast, the superficial parts of the tract contain mainly fine diameter axons arising from small cells in the whole contralateral retina, and a small proportion of large diameter axons arising from large, alpha cells in the whole contralateral retina and in the ipsilateral temporal retina. The likelihood that axons from the temporal retina will project contralaterally therefore increases as development proceeds, since these axons are found in the superficial parts of the tract only. This suggests that a time-dependent signal that weakens with age is responsible for directing early arriving optic axons from the temporal retina to take an exclusively uncrossed course.

Animals

The early development of retinal ganglion cells with uncrossed axons in the mouse: retinal position and axonal course.

The carbocyanine dye, DiI, has been used to study the retinal origin of the uncrossed retinofugal component of the mouse and to show the course taken by these fibres through the optic nerve and chiasm during development. Optic axons first arrive at the chiasm at embryonic day 13 (E13) but do not cross the midline until E14. After this stage, fibres taking an uncrossed course can be selectively labelled by unilateral tract implants of DiI. The earliest ipsilaterally projecting ganglion cells are located in the dorsal central retina. The first sign of the adult pattern of distribution of ganglion cells with uncrossed axons located mainly in the ventrotemporal retina is seen on embryonic day 16.5, thus showing that the adult line of decussation forms early in development. A small number of labelled cells continue to be found in nasal and dorsal retina at all later stages. At early stages (E14-15), retrogradely labelled uncrossed fibres are found in virtually all fascicles of the developing nerve, intermingling with crossed axons throughout the length of the nerve. At later stages of development (E16-17), although uncrossed fibres pass predominantly within the temporal part of the stalk, they remain intermingled with crossed axons. A significant number of uncrossed axons also lie within the nasal part of the optic stalk. The position of uncrossed fibres throughout the nerve in the later developmental stages is comparable to that seen in the adult rodent (Baker and Jeffery, 1989). The distribution of uncrossed axons thus indicates that positional cues are not sufficient to account for the choice made by axons when they reach the optic chiasm.

Animals

Normal and abnormal visual field maps in albinos. Central effects of non-matching maps.

The abnormal chiasmatic crossing characteristic of all albino mammals brings two discordant representations of the visual field to the central visual relays. The representation from the nasal retina is normal whereas the one from the temporal retina is disrupted, a part representing the contralateral visual field as is normal and a part coming from the ipsilateral visual field as a mirror image of a part of the normal representation. Experiments that were designed to define the rules on the basis of which the abnormal representations can be established in the lateral geniculate nucleus and visual cortex are described. These experiments are related to more recent studies of albino cats, and the observations of the visual pathways are related speculatively to abnormalities seen in the auditory pathways of albinos. The possibility is raised that the auditory abnormalities are secondary to the visual abnormalities, produced by a failure of the two systems to establish normally matching maps of sensory space.

Albinism

Evidence for the delayed expression of a brainstem abnormality in albino ferrets.

Previous reports have suggested that neurons of the medial superior olivary nucleus in albino cats and rabbits are smaller than those in normally pigmented strains. In this investigation, the mean cross-sectional areas of neuronal perikarya in the medial superior olivary nucleus of pigmented and albino ferrets were compared at juvenile (14 weeks) and adult (greater than six months) ages. The mean cross-sectional area of the perikarya in adult albino ferrets was found to be 45% smaller than that of adult pigmented ferrets, confirming observations in cat and rabbit. The same comparison in juvenile ferrets, however, showed no significant differences. These results suggest that the mechanisms producing the abnormality of the auditory pathways differ from those responsible for the production of abnormal retinofugal pathways in albinos.

Albinism

Early monocular enucleations in fetal ferrets produce a decrease of uncrossed and an increase of crossed retinofugal components: a possible model for the albino abnormality.

The terminal distributions of retinofugal axons to geniculate laminae or cell groups have been studied in monocular ferrets that had had one eye removed on the 28th or 29th day of intrauterine life and survived until the end of the fourth postnatal week. Normally pigmented and albino animals were studied and the patterns of retinogeniculate terminations in these were compared with earlier accounts of the patterns that develop normally or after a monocular enucleation on the day of birth. Birth normally occurs after 41 days of gestation. In albino animals the neonatal and prenatal enucleations produce essentially the same result. The abnormally large crossed retinogeniculate component, which is also characteristic of normal adult albinos, innervates the major (A) laminae and these fuse medially and caudally as in normal albinos. These represent geniculate Layers A and A1. The abnormally small uncrossed component resembles the abnormally small uncrossed component of normal albinos in innervating several separate terminal islands within the geniculate region. These are larger than in a normal albino animal and are surrounded by a zone of sparser termination not seen in a normal albino. In normally pigmented animals the prenatal enucleation produces a result essentially like that produced by the enucleation in albinos, whereas the postnatal enucleation produces a relatively more symmetrical retinogeniculate pathway in which the crossed component innervates an abnormally enlarged Lamina A and the uncrossed component innervates an enlarged Lamina A1. These results can be most readily explained by assuming that between embryonic Day 28 and the day of birth there is an interaction between the two retinofugal pathways that produces an increase in the uncrossed component from the levels characteristic of albinos and early monocular enucleates to normal levels. This interaction must then be absent in albinos.

Albinism

The beta sector of the rabbit's dorsal lateral geniculate nucleus.

The beta sector of the rabbit's dorsal lateral geniculate nucleus is a small region of nerve cells scattered among the fibres of the geniculocortical pathway. In its topographical relations it resembles the perigeniculate nucleus of carnivores, which contains neurons driven by geniculate and visual cortical neurons and which sends inhibitory fibres back into the geniculate relay. We have traced retinogeniculate, geniculocortical and corticogeniculate pathways in rabbits by using horseradish peroxidase or radioactively labelled proline and have found that the beta sector resembles the perigeniculate nucleus in receiving no direct retinal afferents, sending no efferents to the visual cortex (V-I), and receiving afferents from the visual cortex. The corticogeniculate afferents are organized so that the visual field map in the beta sector and the main part of the lateral geniculate relays are aligned, as are the maps in the cat's perigeniculate nucleus and the main part of the geniculate relay of carnivores. Electron microscopical studies show similar types of axon terminals in the rabbit and the cat for the main part of the geniculate relay on the one hand and for the beta sector and the perigeniculate nucleus on the other. Earlier observations that the proportion of putative inhibitory terminals (F-type terminals) is lower in the rabbit's than the cat's geniculate region are confirmed. A major difference between the beta sector and the perigeniculate nucleus has been revealed by immunohistochemical staining for GABA. Whereas almost all of the cat's perigeniculate cells appear to be GABAergic, the proportion in the beta sector is much lower, and not significantly different from that found in the main part of the rabbit's geniculate relay. It is concluded that the beta sector shares many of the organizational features of the perigeniculate nucleus. A common developmental origin seems probable, but the functional differences remain to be explored.

Animals

Changing glial organization relates to changing fiber order in the developing optic nerve of ferrets.

The structures of the developing eye-stalk and the relationships of early retinofugal fibers as they pass through the stalk, chiasm, and tract have been studied by light and electron microscopical methods in fetal ferrets aged 23-27 days. The early eye-stalk can be divided into two parts: a narrow extracranial part has a narrow lumen and is lined by few cells, whereas a thicker intracranial part has a wider lumen and is lined by several rows of cells. At the earliest stages no axon bundles are recognizable in the stalk, but fibers of the supraoptic commissure are already beginning to cross the midline in the diencephalon. Subsequently, as retinofugal axons invade the stalk, the glia of the extracranial part of the stalk have an interfascicular distribution and axon bundles are separately encircled by glial cytoplasm. In the intracranial part, as in the chiasm and tract, the glial cells occupy a periventricular position and send slender radial cytoplasmic processes to the subpial surface; these pass between groups of axons that here lie immediately deep to the subpial glia. Whereas axonal growth cones have no evident preferred distribution in the extracranial stalk, they tend to accumulate near the pial surface intracranially. The boundary between the two types of organization shifts as development proceeds so that the interfascicular glial structure of the early extracranial stalk first encroaches upon the intracranial parts and later appears in the chiasm. The characteristic adult arrangement of fibers in an age-related order in the optic chiasm and tract, but not in the optic nerve, can be understood if axonal growth cones are guided toward the pial surface by radial glia but not by interfascicular glia. From the distribution of the growth cones, this is what appears to happen.

Animals

Early uncrossed component of the developing optic nerve with a short extracerebral course: a light and electron microscopic study of fetal ferrets.

During the study of the developing optic nerve described in the preceding paper (Guillery and Walsh, '87), small bundles of nerve fibers were seen passing between the optic nerve and the ipsilateral hypothalamus of 24-to 27-day-old prenatal ferrets. The bundles appear before any other fiber groups of the retinofugal pathway and are identifiable while the main portions of the retinofugal system are growing into the optic tracts. The bundles, made up of 50 or more axons, leave the optic nerve, emerge through the otherwise continuous layer of subpial glia and through the basal lamina of the nerve, run a short, naked, extracerebral course among collagen fibers and presumed fibroblasts, and then re-enter the central nervous system, passing rostrally and dorsally to the superficial parts of the ipsilateral hypothalamus away from the region of the chiasm. These fibers represent the earliest link between the optic nerve and the brain, but their course is not followed by the majority of retinofugal fibers developing later, which pass toward one or the other optic tract.

Animals

Distribution of axons according to diameter in the monkey's optic tract.

The distribution of axonal diameters in the optic tract of Old World monkeys was examined by light and electron microscopy. Axon diameters were measured in samples of 100 axons taken from several locations in a cross section of the tract about 5 mm behind the optic chiasm. Fine-caliber axons (less than 1.75 micron in diameter) were found in all parts of the tract. Dorsally no coarse axons were present. Further ventrally, coarse axons gradually appeared and increased steadily in proportion. The largest optic axons (greater than 2.5 micron) were found in the most ventral parts of the tract, near the pial surface. This pattern of segregation of axons of differing diameters in the optic tract is a rearrangement of the distribution of axon diameters seen in the nerve rather than a continuation of the same pattern. Examination of axon diameters in the optic nerve has shown that there is a preponderance of fine axons centrally, while coarser axons are found in the periphery, near the pial surface; however, histograms from central parts of the nerve contain a greater proportion of coarse axons than the dorsal parts of the optic tract, while histograms from the periphery of the optic nerve contain a conspicuously greater proportion of fine axons than do histograms from the most ventral parts of the tract. This relatively greater segregation of axons according to diameter in the optic tract demonstrates that the distribution of axons in the tract cannot be formed by the simple combination of two hemiretinal maps contained in each optic nerve, as suggested in classic descriptions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Abnormally high variability in the uncrossed retinofugal pathway of mice with albino mosaicism.

Female mice showing albino mosaicism due to an X-autosome translocation [Is(In7;X)Ct] have been studied in order to investigate the relationship between the distribution of melanin and the formation, early in development, of the abnormally small uncrossed retinofugal pathway characteristically found in all albino mammals. Earlier evidence indicates that cells normally bearing melanin play a role in producing the abnormality. In the mosaic mice, the albino gene is expressed in only about half of the cells due to random X-inactivation and the patches of normal and albino cells are extremely small relative to total retinal size (less than 1/50). We argued that if all the cells that would normally bear melanin play a role in producing the albino abnormality then the mosaic mice would have a pathway abnormality, about half the size of that in the albino mice. If, however, only a small patch of these cells plays a role, as has been proposed in earlier studies, then one would expect the size of the uncrossed pathway to be highly variable in the mosaic mice. The size of the uncrossed pathway was assessed by placing horseradish peroxidase in the region of the optic tract and lateral geniculate nucleus unilaterally and then counting the number of retrogradely labelled retinal ganglion cells on the same side. The mosaic mice showed a highly variable uncrossed pathway. In some of the mosaic mice, it was the same size as in the albinos and, in others, it was the same size as in normally pigmented mice. Surprisingly, in a small number of mosaic mice, the uncrossed pathway was larger than normal. Whether this relatively rare occurrence of a supernormal uncrossed pathway is due to the higher gene dosage or to the translocation itself remains an open question.

Albinism

A demonstration of two distinct geniculocortical projection patterns in albino ferrets.

The geniculocortical pathways of albino ferrets have been studied by injecting lectin bound horseradish peroxidase into the visual cortex and then studying the geniculate distribution of retrogradely labelled cells in the dorsal lateral geniculate nucleus. It has been shown that in ferrets, as in Siamese cats, there are two quite distinct patterns of geniculocortical projection. One of the patterns seen in ferrets is comparable to the 'Midwestern' pattern previously described in Siamese cats, while the other is comparable to the 'Boston' pattern.

Albinism

The organization of the lateral geniculate nucleus and of the geniculocortical pathway that develops without retinal afferents.

The fine structure and cortical connections of the dorsal lateral geniculate nucleus have been studied in postnatal (3.5-14-month-old) ferrets in which all retinal afferents had been removed prenatally at the time these fibers are first starting to invade the nucleus. The synaptic profiles in the mature nucleus show the cytological characteristics and arrangements that would remain if the retinal afferents were removed, with no significant compensatory ingrowth of foreign specific afferents. The nucleus is reduced in overall volume, but the geniculocortical and corticogeniculate interconnections show an essentially normal topography. Although in these experiments the geniculocortical projections can establish a normal topographic pattern in the absence of retinal afferents an accompanying paper shows that this topographic pattern can also be modified in the presence of abnormal retinogeniculate inputs. We conclude that two separate mechanisms contribute to the formation of retinal maps within the geniculocortical pathways and that different interactions between these two mechanisms produce the different patterns of abnormal geniculocortical pathways that have been described in pigment-deficient cats, mink and ferrets.

Animals

Age-related fiber order in the optic tract of the ferret.

In the ferret's optic tract, the position of retinofugal fibers has been related to their relative age by preferentially labeling the oldest fibers. It has been found that fiber order perpendicular to the pial surface represents the sequence of axon arrivals in the optic tract, the fibers furthest from the pia being the oldest. Immature ferrets, less than 34 days post-conception (E34), were given intravitreal injections of lectin-bound horseradish peroxidase or of 3H-amino acids. After survival times of 24 hr or less, the contralateral optic tract was uniformly labeled, whereas with longer survival times unlabeled zones were seen next to the pial border. These unlabeled zones were largest after injections into the youngest animals but were never seen when injections were made after E34, no matter what the survival time. The unlabeled zones were seen in the tracts of animals having unlabeled regions in the periphery of the retina. The unlabeled retinal ganglion cells are interpreted as ganglion cells formed after the injection was made, and unlabeled axons next to the pia in the tract are interpreted as the axons of these youngest cells. Some irregularities in the layered arrangement of the tract are described, and the fiber order in the tract is contrasted with that in the optic nerve behind the eye. It is shown that tract order is partially independent of order in the intraorbital part of the optic nerve. Between the retina and the optic tract, a sorting of fibers occurs not only in terms of the pattern of decussation, but also in terms of fiber age.

Aging

The influence of retinal afferents upon the development of layers in the dorsal lateral geniculate nucleus of mustelids.

The extent to which the development of a normal laminated lateral geniculate nucleus depends upon retinal afferents has been studied in normal and albino ferrets and in mink. Removal of all retinal afferents before they invade the nucleus (28 days in utero) or before they establish distinct monocular terminal fields (newborn, approximately 41 days post-conception) produces a nucleus that is smaller than normal and poorly separated from the adjacent perigeniculate and medial interlaminar nuclei. However, the nucleus is wedge-shaped, resembling a normal adult nucleus, in which a broad medial binocular segment is distinguishable from a narrower lateral monocular segment. There is a normal mediolateral gradient of cell sizes and some signs of a laminar differentiation, cells next to the optic tract being morphologically distinguishable from cells near the optic radiation, but no cell-free interlaminar zones are formed. The development of a monocularly innervated nucleus depends on the size of the surviving retinal input. In normally pigmented ferrets or mink the crossed retinofugal component is larger than the uncrossed component. In the monocular animals one sees essentially a monocular set of geniculate layers on each side, with an appropriate asymmetry. Each nucleus can be regarded as representing the survival of those layers which would have been innervated by the good eye, together with some additional geniculate territory that appears to be added to the surviving layers as retinogeniculate axons occupy territory normally innervated by the other eye. The crossed component of an albino ferret is abnormally large and the monocularly innervated contralateral nucleus is almost like that of a normal albino. There is a full complement of geniculate layers and interlaminar zones, which appears to develop without any binocular interactions. The ipsilateral retinogeniculate component of albinos is extremely small. In the monocular albino animals it forms discontinuous terminal patches, leaving sectors of the poorly differentiated nucleus uninnervated. These results show that in geniculate development there is a limited interaction between the two sets of retinal afferents. Each set plays a well defined and distinctive role, and one can replace the other to a limited extent only.

Afferent Pathways

The development of the retinogeniculate pathways in normal and albino ferrets.

The retinogeniculate pathways of normal and albino ferrets have been studied with horseradish peroxidase and tritiated proline used as axonal markers. The uncrossed retinogeniculate projection of adult albino ferrets is abnormally small and occupies only a fraction of the geniculate area normally occupied by uncrossed afferents. The crossed pathway is correspondingly expanded, occupying almost the entire nucleus. The geniculate laminae in the albino ferret are abnormal, showing abnormal fusions between layers receiving crossed input and abnormal discontinuities next to the small cell islands receiving uncrossed afferents. In early development, retinofugal fibres can be labelled within the optic tracts on the 28th intrauterine day and a few crossed fibres can be traced into the lateral geniculate nucleus. At this stage, the uncrossed component is extremely small in normal and albino animals and cannot be traced beyond the tract. By day 32 retinal fibres are invading the lateral geniculate nucleus bilaterally, the invasion by the crossed component being significantly more advanced than that by the uncrossed component. The uncrossed pathway of the albinos is already abnormal in terms of its size, in terms of the position it occupies in the optic tract, and in terms of its limited invasion of the lateral geniculate nucleus. The abnormally reduced size of the uncrossed component appears earlier than the abnormal segregation of the retinogeniculate terminals, suggesting that the primary action of the albino gene upon central visual pathways is prechiasmatic. At postnatal stages (41 days after conception and older) the normal, gradual withdrawal of the uncrossed fibres from the monocular segment, and the separation of crossed from uncrossed retinogeniculate terminal arbors is significantly delayed in the albinos. The uncrossed retinogeniculate terminals are abnormally sparse initially and become distributed in an abnormal, interrupted pattern as development proceeds. The abnormal pattern of geniculate lamination appears to be secondary to the abnormal distribution of retinogeniculate afferents.

Albinism