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Biomedical subjects

R W Guillery

Publications and source records attributed to R W Guillery.

At least 19 recordsLinked to original sources
PubMed1999

Visual abnormalities in albino wallabies: a brief note.

Abnormally reduced uncrossed retinofugal pathways and abnormally low retinal cell densities have been described in albinos of a number of species of eutherian mammal, but have not been studied in marsupials. The optic chiasm of marsupials differs from that of the eutherian brains that have been studied, with uncrossed fibres segregating from crossed fibres prechiasmatically in the marsupials, but not in the eutherians. We have examined the optic chiasm and the retina in albino and normally pigmented wallabies (Macropus rufogriseus) to determine whether the abnormalities found in eutherian albinos are also present in this marsupial. The uncrossed pathway of the albino wallaby is smaller than that of the pigmented animals and the cell density in the retinal ganglion cell layer is reduced at the area centralis. We conclude that the characteristic albino abnormalities are present in both groups of mammals in spite of the other known differences in the visual pathways. The albino mutation acts at the chiasm in a similar manner in both groups even though the determinants of the chiasmatic pathway differ.

Albinism↗
PubMed1998

On the actions that one nerve cell can have on another: distinguishing "drivers" from "modulators".

When one nerve cell acts on another, its postsynaptic effect can vary greatly. In sensory systems, inputs from "drivers" can be differentiated from those of "modulators." The driver can be identified as the transmitter of receptive field properties; the modulator can be identified as altering the probability of certain aspects of that transmission. Where receptive fields are not available, the distinction is more difficult and currently is undefined. We use the visual pathways, particularly the thalamic geniculate relay for which much relevant evidence is available, to explore ways in which drivers can be distinguished from modulators. The extent to which the distinction may apply first to other parts of the thalamus and then, possibly, to other parts of the brain is considered. We suggest the following distinctions: Cross-correlograms from driver inputs have sharper peaks than those from modulators; there are likely to be few drivers but many modulators for any one cell; and drivers are likely to act only through ionotropic receptors having a fast postsynaptic effect whereas modulators also are likely to activate metabotropic receptors having a slow and prolonged postsynaptic effect.

Animals↗
PubMed1998

Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1.

BACKGROUND: Neural cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) have been implicated in both the fasciculation and guidance of axons, but direct genetic evidence of a role for neural IgCAMs in axon guidance in vertebrates is lacking. The L1 subfamily of vertebrate neural IgCAMs function as both homophilic and heterophilic receptors for a variety of cell-surface and extracellular ligands and may signal through intracellular kinases or by recruitment of the fibroblast growth factor receptor. L1 itself has been implicated in many neural processes and is expressed widely in the embryonic and adult nervous systems. In humans, mutations in the L1 gene are linked with a spectrum of brain disorders, including loss of the corticospinal tract, but the mechanistic basis for these disorders is unknown. RESULTS: We show that mice that do not express L1 have defects in the guidance of axons of the corticospinal tract, a major motor control pathway projecting from the cortex to the spinal cord. Although the pathway to the caudal medulla appears normal, a substantial proportion of axons fail to cross the midline to the opposite dorsal column as normal. In adults, this results in a reduced decussation and in large numbers of axons projecting ipsilaterally. There is also a varying, but reduced, number of corticospinal axons in the dorsal columns of the spinal cord. These do not project beyond cervical levels. We show that these are defects in axon guidance, because they arise during the early stages of the development of the decussation. The presence of a ligand for L1, CD24, specifically at the point of decussation suggests a mechanism in which L1 functions to guide corticospinal axons across the midline. CONCLUSIONS: L1 function is necessary for the guidance of corticospinal axons across the pyramidal decussation in mice. Some of the defects in the corticospinal tract of humans with mutations in L1 could be due to errors in axon guidance at the pyramidal decussation.

Animals↗
PubMed1998

Paying attention to the thalamic reticular nucleus.

The thalamic reticular nucleus can be divided into a number of sectors, each concerned with a different function (sight, touch, hearing, movement or 'limbic' functions). Each sector is connected to more than one thalamic nucleus and to more than one cortical area, and each sector has topographically mapped connections with the thalamus and the cortex. We consider the known details of these connections and show: (1) that they are not the same for each sector; (2) that the reticular nucleus serves as a nexus, where several functionally related cortical areas and thalamic nuclei can interact, modifying thalamocortical transmission through the inhibitory connections that go from the reticular cells to thalamic relay cells; and (3) that we need much more detailed information about these highly organized connections before we can understand exactly how the thalamic reticular nucleus might be influencing thalamocortical pathways in attentional mechanisms or in other, as yet undefined, roles.

Animals↗
PubMed1998

The changing pattern of fibre bundles that pass through the optic chiasm of mice.

The organization of retinofugal fibres in the developing and adult mouse has been studied with transmission electron microscopy, autoradiography and the Bodian silver method. It has previously been shown that all retinal ganglion cell axons are in glial-wrapped bundles in the developing and adult optic nerve, but are not in similar bundles close to the chiasm. In the embryonic mouse this region shows a transition in glial morphology from an interfascicular to a radial type and here retinofugal fibres begin to form a new order related to their age. Growth cones become concentrated at the pial surface of the juxtachiasmatic nerve and older fibres are restricted to deeper regions. This same age-related order is also evident in the optic tract. However, the age-related order is lost within the chiasm, where growth cones, young and old fibres are again mingled in distinct bundles as they cross the mid-line. This study is particularly concerned with the structure of the mid-line bundles. These fibre bundles cross each other at right angles, and are recognizable in fetal and adult mice. In the adult, monocular injections of H3 proline followed by autoradiographic study show that the individual mid-line bundles are monocular and that they fuse again, losing the fascicular structure as they leave the chiasm and enter the tract. In the fetus and in the adult, the bundles generally lack a complete glial wrapping so that growth cones can lie in intimate contact with two crossing bundles, one coming from the left eye, the other from the right. The interesting question about the mechanisms that keep growth cones from entering the wrong bundles when they are in this position remains to be addressed.

Animals↗
PubMed1997

Membrane specializations in the developmentally transient perireticular nucleus of the rat.

The perireticular nucleus lies among the fibres of the internal capsule and in the rat is relatively large at birth. Like the subplate of the neocortex, it is dramatically reduced in the adult (Mitrofanis, 1992). On embryonic day 17 (E17), cells of the perireticular nucleus project to the cortex (Adams and Baker, 1995); at birth there is also a projection to the thalamus (Mitrofanis and Baker, 1993). When corticofugal axons reach the perireticular nucleus, they separate into the descending tracts and the corticothalamic pathway. The axons then enter the internal capsule on their way to the thalamus, defasciculate and contribute to a complex zone of interweaving fibres seen in this region (Adams and Guillery, 1994). We have found that the cells of the perireticular nucleus are immunopositive for an antibody (3A10) to a phosphorylated neurofilament protein (Yamada et al., 1991), and we have shown that these 3A10-positive perireticular cells extend their dendrites across the path of cortical fibres at the earliest age studied (E17). We have confirmed this dendritic orientation by Golgi staining at a later stage (P3). Electron micrographs show that axo-somatic and axo-dendritic synapses first appear in the perireticular nucleus at about the day of birth. Prenatally, between E14 and E19, the major specialized membrane interrelationships seen are omega formations between adjacent profiles that often contain vesicles. Omega formations are rarely seen at later stages. Puncta adhaerentia typified by opposing membrane densities with no associated vesicles were seen at all ages studied. We suggest that early membrane contacts (omega formations) may represent transient organisational or guidance influences since they occur during a period when axonal pathways are being defined.

Animals↗
PubMed1997

Complexities in the thalamocortical and corticothalamic pathways.

It is now a century since Kölliker (Handbuch der Gewebelehre des Menschen. Nervensystemen des Menschen und der Thiere, Vol. 2, 6th edn. Engelmann, Leipzig, 1896) described the thalamic reticular nucleus as the 'Gitterkern' or lattice nucleus on the basis of the fibrous latticework that is the characteristic feature of this part of the ventral thalamus and adjacent parts of the internal capsule. We suggest that the fibre reorganization produced in this lattice is a fundamental requirement for linking orderly maps in the thalamus to corresponding cortical maps by two-way thalamocortical and corticothalamic connections; these connections involve divergence, convergence and mirror reversals, which all have to occur between the thalamus and the cortex. Apart from the thalamic reticular nucleus, two transient groups of cells, the perireticular nucleus (located in the internal capsule lateral to the reticular nucleus) and the cells of the cortical subplate, are prominent along the course of axons linking the cortex and thalamus early in development. The functions of these two cell groups are not known. However, since early in development complex patterns of reorganization, defasciculation and crossings occur in the regions of these cells, it is likely that they play a role in creating the latticework of the adult. The latticework that characterizes the thalamic reticular nucleus of mammals can also be identified in the ventral thalamus of non-mammalian brains, formed along the course of the fibres that join the dorsal thalamus to the telencephalon. We suggest that the ubiquitous presence of such a zone of fibre reorganization is integral to the functioning of the thalamocortical pathways, and that the complexity of thalamic connections produced in the lattice has been central to the evolutionary success of the thalamotelencephalic system.

Animals↗
PubMed1996

The course and termination of corticothalamic fibres arising in the visual cortex of the rat.

Corticothalamic axons have been studied in adult Lister hooded rats with single or dual injections of tracers into the visual cortex. Labelled axons leave medial and lateral injection sites in separate or partially overlapping bundles along parallel trajectories in the subcortical white matter. In the internal capsule they converge and both bundles enter roughly the same sector of the thalamic reticular nucleus (TRN). Their reticular terminal fields, however, differ. Axons from a medial injection site innervate more lateral parts of the TRN than do the axons from lateral injection sites. The most medial third of the TRN is not innervated from area 17 but receives a topographically arranged input from peristriate cortex (Crabtree and Killackey, 1989, Eur. J. Neurosci., 1, 94-109; Coleman and Mitrofanis, 1996, Eur. J. Neurosci., 8, 388-404). The two groups of axons then separate in the dorsal thalamus, axons from medial parts of visual cortex turning caudally into lateral regions of the lateral geniculate nucleus, whereas fibres from more lateral cortex continue into medial parts of the nucleus. Connolly and van Essen (1984, J. Comp. Neurol., 226, 544-564) and Nelson and LeVay (1985, J. Comp. Neurol., 240, 322-330) have shown that in the geniculocortical pathway the two groups of fibres cross over in the subcortical white matter, probably in the region of the subplate. We show that the corticothalamic pathway also has a crossing, but it occurs in, or close to, the diencephalon itself, in the region of the perireticular nucleus. This result suggests that each of these pathways, the geniculocortical and the corticogeniculate, may undergo reorganization within distinct cerebral zones, one diencephalic for the corticothalamic axons and the other telencephalic for the thalamocortical axons.

Animals↗
PubMed1996

Functional organization of thalamocortical relays.

The thalamus has long been seen as responsible for relaying information on the way to the cerebral cortex, but it has not been until the last decade or so that the functional nature of this relay has attracted significant attention. Whereas earlier views tended to relegate thalamic function to a simple, machine-like relay process, recent research, reviewed in this article, demonstrates complicated circuitry and a rich array of membrane properties underlying the thalamic relay. It is now clear that the thalamic relay does not have merely a trivial function. Suggestions that the thalamic circuits and cell properties only come into play during certain phases of sleep to effectively disconnect the relay are correct as far as they go, but they are incomplete, because they fail to take into account interesting and variable properties of the relay that, we argue, occur during normal waking behavior. Although the specific function of the circuits and cellular properties of the thalamic relay for waking behavior is far from clear, we offer two related hypotheses based on recent experimental evidence. One is that the thalamus is not used just to relay peripheral information from, for example, visual, auditory, or cerebellar inputs, but that some thalamic nuclei are arranged instead to relay information from one cortical area to another. The second is that the thalamus is not a simple, passive relay of information to cortex but instead is involved in many dynamic processes that significantly alter the nature of the information relayed to cortex.

Afferent Pathways↗
PubMed1995

Effect of a very early monocular enucleation upon the development of the uncrossed retinofugal pathway in ferrets.

Monocular enucleations were done in ferret embryos before or during the earliest stages of development of the retinofugal pathway (E23-E26). The effects on the development of the uncrossed pathway from the surviving eye were assessed on embryonic day 30. This stage was chosen for two reasons: (1) we show that in normal development a substantial uncrossed component from the temporal crescent has developed by E30; and (2) the pathway cannot yet have been affected by the cell death that normally occurs in the retina in the perinatal period. Using DiI labelling from either the temporal crescent or the optic nerve head, we have shown that such early enucleations prevent the formation of the uncrossed pathway from the temporal crescent of the surviving eye. Enucleation at E23/24, before or during the period when the first axons reach the chiasm, prevents the formation of the uncrossed projection. The axons that would normally take an uncrossed course stall lateral to the midline of the optic chiasm. At E26, when many axons have reached the optic chiasm, but none yet come from the temporal crescent, enucleation causes a dramatic reduction in the uncrossed projection, and the complete abolition of the normal uncrossed pathway from the temporal crescent. This demonstrates that there is a requirement for an interaction between the axons of the two eyes at the optic chiasm to establish the normal formation of the uncrossed pathway at the optic chiasm.

Animals↗
PubMed1995

A note on the relative rates of degeneration in the crossed and the uncrossed retinofugal fibres in the opossum Didelphis marsupialis.

The rates at which the crossed and the uncrossed components of the retinofugal pathway degenerate in Didelphis has been studied by light and electron microscopical methods. We have found that in Didelphis, as in Monodelphis the two components can be clearly distinguished at the level of the chiasm. However, in contrast to the situation previously described for Monodelphis, where the uncrossed component degenerates more rapidly than the crossed, both components degenerate at the same rate.

Animals↗
PubMed1995

Developmental determinants at the mammalian optic chiasm.

The mammalian optic chiasm is widely and properly regarded as a region where axons from the temporal retina take an uncrossed course and separate from axons arising in the nasal retina that take a crossed course. However, this is but a rough approximation of the adult situation, and developmental studies must take account of several distinctive stages and axon rearrangements that characterize the region of the chiasm. At the early and late stages of development of nonprimate species the axons do not segregate in accordance with a strict naso-temporal rule at all, and their behavior at the chiasm is not relevant to the formation of the naso-temporal division. As the axons pass from the eye to the chiasm they tend to lose their retinotopic order, to gain a chronotopic order, and then, in the region of the chiasm, to regain some aspects of the retinotopic order before reaching their terminal sites. Molecular or cellular cues that allow the several distinct organizational steps to occur must be expected in the retina, on the axons themselves, and also along the pathway of the axons, prechiasmatically and at the chiasm. Some of these cues will be associated with local nerve cells, some with specialized glial elements and some with the retinofugal axons themselves. Several candidate molecules have been identified in the retina and along the path of the axons, but to date no clearly defined role in the specific events of the pathway determination have been identified. The sequence of developmental processes that characterizes the formation of the optic chiasm provides an interesting and useful challenge to experimentalists, because the advancing axons can now be observed in vitro and in the living brain. The pattern of growth changes as development proceeds, it shows distinctive properties in different species and in their genetic mutants, and it can be readily modified by simple experimental procedures. These all provide opportunities for investigating the function of proposed molecular cues that act in the development of the chiasm.

Animals↗
PubMed1995

Does early monocular enucleation in a marsupial affect the surviving uncrossed retinofugal pathway?

Monocular enucleations have been done during early stages (postnatal days 3 to 9) of visual system development of Monodelphis domestica, in order to determine whether in this marsupial, as in several eutherian mammals, there are any interactions between the pathways from the two eyes in establishing the uncrossed retinofugal projection. We have examined the distribution and the number of retrogradely labelled ganglion cells that project to the same side of the brain from the surviving eyes shortly after the uncrossed pathway is first formed in normal development (postnatal days 14 to 28). Even at these early stages of development the surviving uncrossed pathway shows no significant reduction, confirming earlier observations of adult marsupials and showing that at no stage in development is there any evidence that the crossed pathway from one eye influences the navigation of axons that will form the uncrossed pathway from the other eye. This is in sharp contrast to observations of mice, rats and ferrets and is in accord with expectations based on the difference of the chiasmatic structure in marsupials as compared with eutherians.

Animals↗
PubMed1995

Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review.

Two distinct types of thalamic nucleus are proposed on the basis of the afferent fibres that they receive from ascending pathways and from the cerebral cortex. 'First order nuclei' receive primary afferent fibres, definable on the basis of their origin and their intrathalamic synaptic relationships, from ascending pathways. These nuclei receive corticothalamic afferents from pyramidal cells in cortical layer 6, which also send branches to the thalamic reticular nucleus and appear to have a modulatory function. 'Higher order nuclei' receive most or all of their 'primary afferents' from pyramidal cells in cortical layer 5. These resemble the ascending primary afferents in the first order nuclei in terms of fine structure, synaptic relationships and in lacking a branch to the thalamic reticular nucleus. The higher order nuclei also receive modulatory afferents from layer 6. It is proposed that the higher-order nuclei are largely concerned with transmitting information about the output of one cortical area to another cortical area, and that they are likely to play a key role in corticocortical communication and higher cortical functions.

Cerebral Cortex↗
PubMed1995

A comparison of eutherian and marsupial optic chiasms: a brief review.

There are four fiber components in the mammalian optic chiasm. Two crossed and two uncrossed components, one of each from each eye. The two crossed components meet at the midline, forming coarse interdigitating bundles in some species, and extremely fine crossing bundles in others. The two components from one eye mingle in the optic nerve. Then in some species they separate, before reaching the chiasm, but in others they do not separate until they reach the midline of the chiasm. Once past the chiasm, the two components that form the tract reunite and one more, the crossed and the uncrossed fibers mingle. The review considers that difference between the marsupial and the eutherian mammals that have been studied, and looks at the developmental changes that are likely to underlie these different types of chiasmatic organization.

Animals↗