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Biomedical subjects

R W Guillery

Publications and source records attributed to R W Guillery.

At least 73 records · Page 4Linked to original sources

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↗

Abnormal central visual pathways in the brain of an albino green monkey (Cercopithecus aethiops).

The visual pathways of an albino green monkey have been studied electrophysiologically and by autoradiographic methods. The monkey had a white coat and pink eyes; it had a strabismus and a nystagmus. When comparisons were made with normal macaque and green monkeys, several abnormalities could be defined. In the retina there was no foveal pit. A whole mount preparation showed a central area of high ganglion cell density in which the ganglion cells were significantly larger than the most central ganglion cells of a normal monkey. More peripheral retinal areas showed an apparently normal distribution of ganglion cell sizes and packing densities. Within the optic tract the number of uncrossed retinofugal fibers was less than normal, the part of the tract that represents central vision showing almost no uncrossed component. The uncrossed input to the lateral geniculate nucleus and to the superior colliculus was similarly reduced. Regions normally receiving ipsilateral afferents from the central retina were innervated exclusively by crossed afferents. The pathways to the magnocellular geniculate layers showed a more extensive abnormality than did the pathways to the parvicellular layers. Not only were the afferents to the geniculate layers abnormal, but the laminar pattern in the nucleus was also clear than normal in some parts of the nucleus, and there were a number of abnormal laminar fusions. Within the visual cortex it was possible to demonstrate a normal mapping of the contralateral visual field through the contralateral nasal retina and through the peripheral parts of the ipsilateral temporal retina. The central parts of the temporal retina mapped abnormally in the contralateral visual cortex, so that there was a monocular map of the central parts of the visual field forming as a mirror reversal of the normal map. The normal map of the contralateral hemifield formed columns that alternated with the abnormal map of the ipsilateral hemifield. The peripheral parts of the visual field were represented as ocular dominance columns, demonstrable electrophysiologically and also by the transneuronal transport of 3H-proline.

Animals↗

The organization of retinal maps within the dorsal and ventral lateral geniculate nuclei of the rabbit.

The cytoarchitectonic subdivisions in the rabbit's dorsal and ventral lateral geniculate nuclei have been related to the several retinal maps that can be defined in terms of the distribution of retinal axons within these nuclei. Destruction of different retinal sectors was combined with intravitreal injections of 3H-proline, so that the distribution of fiber degeneration and autoradiographic label in the geniculate nuclei could be used to define the retinal maps in each nucleus, and to compare the two nuclei with each other. The two nuclei show surprisingly similar patterns of organization. Each is made up of a laminated alpha sector that curves around a relatively cell-sparse beta sector. Two morphologically distinct layers of each alpha sector receive contralateral retinal afferents and between these there is a small region in receipt of ipsilateral afferents. In each nucleus, the lines of projection that represent single points in visual space pass perpendicular to the layers of the alpha sector and continue an almost straight course into the beta sector. Quantitative comparisons of the retinal maps show that the relative volumes devoted to the representation of segments of the visual field are approximately the same in the two nuclei.

Animals↗

Nerve terminal degeneration after a single injection of D-amphetamine in iprindole-treated rats: relation to selective long-lasting dopamine depletion.

A single injection of D-amphetamine has recently been shown to produce long-lasting dopamine (DA) deficits in rats pretreated with iprindole, an agent which interferes with the metabolism of amphetamine and prolongs its half-life. The basis for these persistent DA deficits has not been determined. The present results suggest that amphetamine produces prolonged DA depletions in iprindole-treated rats by destroying DA nerve terminals.

Animals↗

Patterns of synaptic contact upon individually labeled large cells of the dorsal lateral geniculate nucleus of the cat.

Four large geniculate cells that were densely filled with horseradish peroxidase have been studied in detail, at first light microscopically, to define the shape and distribution of the dendritic arbors, and then electron microscopically, to define the pattern of synaptic contacts upon their surfaces. Three of the cells had the morphological characteristics of a class 1 cell, and one cell was intermediate between class 1 and 2. All of these cells had few of the characteristic grape-like appendages, thought to receive retinal input within synaptic glomeruli. Retinal afferents were mainly distributed around proximal juxtasomatic dendritic segments and dendritic branch points. Some retinal afferents made simple axodendritic contacts, while others formed a part of a synaptic glomerulus. None of the retinal afferents forming synapses near the perikaryon were involved in glomeruli. Within the glomeruli involving class 1 cells, retinal terminals can relate both to dendritic segments, particularly near branch points, as well as to dendritic appendages. The few singly placed grape-like appendages were always contacted by retinal afferents, but not necessarily in a glomerular arrangement. Terminals interpreted as cortico-geniculate were seen most commonly upon peripheral dendritic segments, while those containing pleomorphic vesicles (F) were distributed more or less evenly over all parts of the dendritic and perikaryal surface. The perikaryon itself was contacted by F-type terminals but was not contacted by retino-geniculate or cortico-geniculate terminals. A class of slender axonal terminal, containing round synaptic vesicles and few or no mitochondria, was found contacting two of the four perikarya, but the origin of these slender axons is unknown. It is concluded that the surfaces of geniculate class 1 cells can be separated into several functionally distinct zones on the basis of the synaptic contacts they receive.

Animals↗

Generation of cat retinal ganglion cells in relation to central pathways.

The ganglion cells of the cat retina form classes distinguishable in terms of perikaryal size, dendritic morphology and functional properties. Further, the axons differ in their diameters, patterns of chiasmatic crossing and in their central connections. Here we define, by 3H-thymidine autoradiography, the order of production of cells of each class and relate the order of the 'birthdates' to the known axonal pathways. The ganglion cell classes are produced in broad waves, which overlap as cells are produced first for central then for peripheral retina. Medium-sized cells are produced before the largest cells, and small ganglion cells are produced throughout the period of cell generation. This sequence of cell production relates to the orderly arrangement of axons in the optic tract, and can also be related to the rules of chiasmatic crossing observed for each ganglion cell class.

Animals↗

Studies of retinal representations within the cat's optic tract.

The manner in which each retina can be mapped onto a single cross section of the optic tract of the cat has been defined by neuroanatomical methods. It has been found that the contralateral nasal hemi-retina and both temporal hemi-retinae are represented in each tract by multiple, rough maps which partially overlap one another. All maps show the same general orientation, with area centralis represented dorsomedially, lower retina represented dorsolaterally, and upper retina represented ventromedially. The peripheral part of the horizontal meridian is represented ventrolaterally. Labeling all of the fibers from one eye by axonal degeneration or autoradiographic methods shows that the crossed map is displaced dorsally and medially relative to the uncrossed map, leaving a dorsomedial crescent of pure crossed fibers. Localized retinal lesions or injections of 3H-amino acid show the general orientation of the maps. Lesions within the dorsomedial pure crossed crescent show that fibers in this crescent arise from retinal areas close to the optic disc, near the site of the early fetal fissure. Localized injections of horseradish peroxidase into the optic tract show the relationships of the several maps in terms of the retinal distribution of retrogradely labeled retinal ganglion cells. They show that axons of large and small cells map ventrolaterally in the tract while intermediate sizes map dorsomedially. They confirm that the crossed map is displaced relative to the uncrossed maps. It is suggested that the optic tract develops by fibers taking a position in the tract in accordance with their time of arrival at the chiasm. The several maps are displaced because they develop sequentially and the optic tract can be read as a developmental record, the most dorsomedial axons being the oldest.

Animals↗

Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain.

Numerous recent studies indicate that when amphetamines are administered continuously or in high doses, they exert long-lasting toxic effects on dopamine (DA) neurons in the central nervous system (CNS). Specifically, it has been shown that amphetamines can decrease the content of brain DA, reduce the number of synaptosomal DA uptake sites and selectively depress the in vitro activity of neostriatal tyrosine hydroxylase (TH). To date, however, anatomical evidence of DA neuronal destruction following amphetamines has not been reported. In this study, chemical methods were used in conjunction with the Fink-Heimer method which allows for the selective silver impregnation of degenerating nerve fibers, in order to determine whether methylamphetamine, a potent psychomotor stimulant often abused by man, causes actual DA neural degeneration. It has been found that methylamphetamine induces terminal degeneration along with correlative DA neurochemical deficits in the neostriatum and nucleus accumbens; furthermore, that in cresyl violet-stained sections of the substantia nigra (SN), pars compacta, and ventral tegmental area (VTA), there is no evidence of cell body loss in rats in which 50-60% of neostriatal DA terminals have been destroyed.

3,4-Dihydroxyphenylacetic Acid↗