Biomedical subjects

G Jeffery

Publications and source records attributed to G Jeffery.

At least 19 recordsLinked to original sources

PubMed1992

Translaminar deficits in the retinae of albinos.

The central retina in albino mammals is poorly developed. There is a general reduction in ganglion cell density compared with the normal animal, and there are irregularities in the center to periphery gradient in ganglion cell density. It is not known whether, and if so to what extent, this abnormality is associated with deficits in other retinal layers. In this study the distribution of cells in the ganglion cell layer has been determined in horizontally sectioned eyes from pigmented and albino ferrets. This was undertaken to define the location of the region of highest cell density and the relative cell gradients around it. Detailed counts and measurements were then undertaken to determine the cell density within, and thickness of, the inner and the outer nuclear layers in these animals. All the albino animals had an abnormal distribution of cells in the ganglion cell layer in the central retina when compared with pigmented animals. The extent of this abnormality was variable. No differences between pigmented and albino animals could be found in the packing density of cells within the inner or the outer nuclear layer. However, in the pigmented animals there was a clear increase in the thickness of these layers associated with the region of highest density in the ganglion cell layer. This feature was absent in the albino animals, where the gradient in layer thickness was less marked and frequently contained irregularities. These abnormalities were most obvious in the outer nuclear layer.

Albinism↗

PubMed1992

Distinctive pattern of organisation in the retinofugal pathway of a marsupial: I. Retina and optic nerve.

The nasotemporal division in the retina and the pattern of crossed and uncrossed axons in the optic nerve were determined in an Australian marsupial, a wallaby, Setonix brachyurus (the quokka), following unilateral horseradish peroxidase injections into primary visual centres. The gross morphology of the nerve was also examined. Ipsilaterally projecting ganglion cells were restricted to the temporal retina, whereas those that project contralaterally were located in all retinal regions. The morphological study of the nerve showed that fasciculation patterns, evident along much of the length of the nerve, became indistinct centrally and were replaced in the prechiasmatic region by dorsoventrally oriented fissures. In this prechiasmatic region, axons were oriented in two directions. Whereas the majority were aligned centroperipherally with the long axis of the nerve, a proportion were aligned dorsoventrally in the fissures. Labelling with HRP revealed that uncrossed axons were restricted to the lateral region of the optic nerve and possibly to discrete fascicles, whereas those destined to cross at the chiasm occupied all regions of the nerve but were less dense on the lateral side. This spatial distribution of crossed and uncrossed projections did not change along the length of the nerve. These results demonstrate that fibre organisation in the marsupial optic nerve is different than that found in eutherian mammals.

Animals↗

PubMed1992

Distinctive pattern of organisation in the retinofugal pathway of a marsupial: II. Optic chiasm.

In the mammalian optic chiasm retinal axons from each eye divide into two populations, those that decussate and those that remain uncrossed. In eutherian (placental) mammals, the separation of these pathways is not reflected in the structure of the chiasm. The two populations from each eye are mixed through each hemichiasm, segregating only at the midline, where the uncrossed projection turns back. In this study the optic chiasm of a marsupial, the wallaby, Setonix brachyurus (quokka) has been investigated with staining and neuronal tracing techniques. The chiasm of this mammal is quite different from that of eutherian mammals. In coronal section it can be morphologically subdivided into three regions, a central body in which fasciculated groups of axons from each eye interdigitate across the midline, and two distinct lateral regions, one on each side, which contain the uncrossed retinal projections. In the rostral chiasm the lateral regions are separated from the main body of the chiasm by vertically oriented fibre-free regions. Caudally, the lateral regions increase in size and become less distinct as increasing numbers of contralaterally projecting axons that have crossed the midline project into them. However, the two populations remain predominantly segregated in this region. As the lateral regions develop, the central body of the chiasm becomes thinner and finally detaches at the midline to form the two optic tracts. The routes taken by retinal axons through the eutherian and marsupial chiasm appear to be fundamentally different. Therefore, the developmental factors that determine the laterality of retinal projections are likely to show significant differences in the two mammalian groups.

Animals↗

PubMed1992

The mosaic of alpha cells in the cat retina is not dependent on axon terminal interactions during development.

Alpha ganglion cells in the cat retina are distributed in a regular array. It has been proposed that the development of this mosaic pattern is achieved by class-specific interactions between the dendrites and/or axon terminals of neighbouring alpha cells, but the relative contributions that are made by each of these factors to the regularity of the mosaic remain unclear. An opportunity to address this question is provided by a comparative study of the distribution of alpha cells across the nasotemporal division of normally pigmented and Siamese cat retinae. In this strip of retina the alpha cell population divides its axon terminals between the two sides of the brain. Hence, the potential for interactions between axon terminals of alpha cells whose somata are adjacent within this region of the retina is undermined. This situation is exacerbated in Siamese cats because they have a congenital abnormality in this region, which results in an abnormally wide nasotemporal division. In this study the regularity of the alpha cell mosaic has been analysed at a wide range of eccentricities, including the nasotemporal division. In normally pigmented cats the nasotemporal division was visualised directly following unilateral horseradish peroxidase injections into the thalamus. In Siamese cats, the location of the abnormally wide nasotemporal division was inferred from electrophysiological recordings undertaken in their striate cortices. In both strains of cat the regularity of the alpha cell mosaic was shown to be largely independent of their density or retinal location. Furthermore, in the normals, the separate mosaics for ipsilaterally or contralaterally projecting alpha cells within the nasotemporal division were found to be no more or less regular than that for the combined population. This finding implies that there is no disturbance in their order across the discontinuity formed by their separate chiasmatic routes. Similar results were obtained from within the abnormal nasotemporal division of the Siamese cat. It is concluded that terminal interactions play an insignificant role in the formation of the adult alpha cell mosaic, the regularity of which is probably established by class-specific intraretinal interactions.

Animals↗

PubMed1992

The fascicular organisation of the cat optic nerve.

Mammalian optic nerve axons are organised within a fascicular framework. This pattern changes between the eye and the chiasm. For most of the length of the nerve fascicular patterns are apparent, but close to the chiasm, in a region of major fibre rearrangement, the fascicular configuration is lost. It is not known how this change occurs, or whether there are less obvious systematic changes in the number of fascicles or their geometry along the length of the nerve. In this study these questions have been addressed at successive locations along the length of the cat optic nerve. The number of fascicles varied depending upon the location examined. A relatively high number were found behind the eye. The number declined in the mid-orbital portion before increasing again in the region of the optic canal. Further caudally there was a progressive change in the pattern of fasciculation, with a loss of fascicular structure medially. The remaining fascicles became concentrated around the inferotemporal periphery of the nerve. There was no fascicular organisation at the point at which the two nerves fused at the chiasm. Although the number of fascicles varied along the length of the nerve their geometric pattern did not change.

Animals↗

PubMed1991

Evaluation of the influence of optic stalk melanin on the chiasmatic pathways in the developing rodent visual system.

In a number of mammalian species, fibre outgrowth in the developing retinofugal pathway is coincident with the presence of melanin in the retinal part of the optic stalk. The presence of melanin is transient in this developing system and has been proposed to play a role in the guidance of retinofugal fibres. Further, it has been suggested that this stalk melanin accounts for the differences between the size of the uncrossed retinal component in pigmented and nonpigmented strains. However, a recent study showed that there is no melanin in the optic stalk of Manchester rats during fibre outgrowth. Since such rats supposedly have a normal pigment distribution and a normal pattern of decussation at the optic chiasm, this finding appears to undermine the suggested role played by stalk melanin in establishing the laterality of retinal fibre projections in other mammalian species. The aim of this study was to re-evaluate the relationship between melanin in the stalk and the development of the retinofugal pathway in three strains of rat: the Wild type, Long Evans Hooded, and the Albino. The Albino rat, which lacks melanin-bearing cells entirely, was shown to have the smallest uncrossed projection, approximately 1,340 ipsilaterally projecting cells (ipc), whereas the Long Evans (2,760 ipc) and the Wild-type strain (2425 ipc) were found to have a larger uncrossed retinal component. In both pigmented strains, melanin was restricted to the eye cup and absent from the optic stalk throughout all stages of development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Albino gene dosage and retinal decussation patterns in the pigmented ferret.

We have examined the retinal decussation patterns in pigmented ferrets that were either wild-type sable or heterozygous with one albino gene. Unilateral injections of horseradish peroxidase were made into the optic tract and labeled ganglion cells visualized in retinal wholemounts. In both wild-type and heterozygous ferrets, those ganglion cells in the temporal retina with the largest cell bodies projected only to the contralateral side of the brain. The total number of ipsilaterally projecting ganglion cells did not differ with the genotype of the animal. The numbers ranged from 5471-6759 cells. Unlike the cat, there is no difference in retinal decussation patterns in wild-type sable ferrets and heterozygous ferrets carrying one albino gene.

Albinism↗

PubMed1990

Early lesion of mystacial vibrissae in rats results in an increase of somatostatin-labelled cells in the somatosensory cortex.

Recent studies in the developing cortex have shown that during the first 2 postnatal weeks somatostatin (SRIF)-containing neurons appear in greater numbers. After this time their numbers decline significantly probably due to cell death (Cavanagh and Parnavelas 1988). In this study we report changes in the distribution of SRIF-labelled cells in the somatosensory cortex of adult rats following unilateral lesions of mystacial vibrissae at birth. Specifically, we observed that the side contralateral to the lesion contained a significantly greater number of labelled cells compared to the ipsilateral side. We suggest that the decline in cell numbers observed during normal development is reduced following early deafferentation.

Animals↗

PubMed1990

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

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

Animals↗

PubMed1990

Distribution of uncrossed and crossed retinofugal axons in the cat optic nerve and their relationship to patterns of fasciculation.

The course of optic axons that take different routes at the chiasm have been traced through horizontally sectioned optic nerves in the cat, after unilateral injections of horseradish peroxide into the optic tract. Behind the eye and for most of the course of the nerve, nearly all of the axons that remain uncrossed at the chiasm are located in a retinotopically appropriate position, in the lateral aspect of the nerve. However, in the most caudal segment of the nerve an increasing proportion of these axons are located in regions that are retinotopically inappropriate. Just before the nerve joins the chiasm, uncrossed axons can be found across the full medio-lateral extent of the nerve, although there is still a relative increase in their density laterally. Labeled axons that cross at the chiasm course in a relatively parallel manner along the greater proportion of the nerve. However, in the caudal segment of the nerve their relative positions change and they appear to course in an irregular manner. This occurs where the uncrossed projection becomes increasingly more widespread. Axons in the optic nerve are grouped into fascicules. This pattern of organization also changes in the caudal region of the nerve. Although clear fascicular patterns are present along the greater part of the nerve, they become progressively less distinct caudally. The change in the pattern of fasciculation occurs over the same region of the nerve as the relative changes in axon trajectory and distribution. These results demonstrate that irrespective of chiasmatic route, optic axons in the cat are reorganized in the caudal segment of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Distribution of uncrossed axons along the course of the optic nerve and chiasm of rodents.

The distribution of the ipsilaterally projecting population of retinofugal axons has been analyzed following injections of horseradish peroxidase (HRP) into the optic tract of adult hamsters and rats to determine whether the topographical segregation of the cells of origin seen in the retina is maintained by their axons throughout the course of the optic nerve and chiasm. Axons are limited to a roughly appropriate topographic location within the intraorbital course of the nerve but this organization changes at levels progressively closer to the optic chiasm. Immediately rostral to the chiasm labelled profiles are found dispersed across most of the cross-sectional area of the nerve. This dispersal is maintained within the region of the optic chiasm where a complex rearrangement of ipsilaterally projecting axons takes place. The results show that axons are not retinotopically organized along the entire length of the optic nerve. The order of axons changes along the course of the nerve and in the optic chiasm. The change seen within the intracranial course may indicate a chronotopic re-sorting of axons prior to the optic tract where the organization of axons has previously been interpreted as a map of time of axon arrival.

Animals↗

PubMed1989

Distribution and trajectory of uncrossed axons in the optic nerves of pigmented and albino rats.

Ipsilaterally projecting axons in the optic nerve of the pigmented rat are limited to a roughly retinotopic location within the intraorbital segment of the nerve. However, immediately rostral to the chiasm they are widely dispersed. Here, the way in which this change in distribution arises is analysed by tracing individual fibers retrogradely labelled from the optic tract with horseradish peroxidase (HRP). A comparison is made between albino and pigmented animals. It is demonstrated that the change in this distribution occurs as a consequence of two types of shift in axon trajectory in the intracranial segment. Many axons change their location in the nerve gradually throughout this segment. However, in the proximal half of this region a number of axons also make abrupt changes in their trajectory by travelling at right angles across segments of the mediolateral axis of the nerve. These were seen in both the pigmented and albino animals. Although the albino has an abnormally small ipsilateral retinofugal pathway, the distribution of ipsilateral axons in the optic nerve is very similar to that seen in pigmented animals. Consequently, it is unlikely that position in the prechiasmatic nerve is related to the chiasmatic choice made by axons in this population.

Animals↗

PubMed1989

Shifting retinal maps in the development of the lateral geniculate nucleus.

During development, the bilateral projections from each eye to subcortical visual structures in the mammal initially overlap throughout the majority of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) before retracting to their separate territories. It has been shown in the ferret that during this period the larger contralateral retinal projection to both the dLGN and SC is retinotopically organised. By making small retinal lesions, and then anterogradely labelling the remaining retinofugal pathway from one eye, this study demonstrates that on the day of birth there is a superficial region of the dLGN in which the retinotopic map cannot be demonstrated. This region may be the presumptive C laminae. Further, by making small lesions in the temporal retina it has been shown that the smaller ipsilateral projection is also retinotopically organised before it retracts. Large lesions confined to the nasal retina had no effect on the pattern of label in the ipsilateral dLGN. Consequently, the ipsilateral projection which fills the nucleus at this stage must arise from the temporal retina. Because of this, the process of segregation requires that the retinotopic maps from each eye shift in relation to one another, and the borders of the nucleus to form the adult pattern.

Animals↗

PubMed1987

Early visual deafferentation of the cortex results in an asymmetry of somatostatin labelled cells.

Biologically active peptides are distributed widely throughout the nervous system. The distribution of each is not random, but follows a relatively specific pattern. Although the time course of development of a number of peptides has been traced, the factors which determine their distribution and function remain unknown. In this study we report changes which occur preferentially in the distribution of one peptide, somatostatin, in the visual cortex of the rat, as a consequence of early unilateral eye removal. Because the uncrossed retinal projection is so small in the rodent, this manipulation substantially reduces the visual innervation of the cortex ipsilateral to the remaining eye, and is correlated here with an asymmetry in the number of somatostatin positive cells.

Animals↗

PubMed1987

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↗

PubMed1986

Are there connections between the thalamic reticular nucleus and the brainstem reticular formation?

Increasing awareness that the thalamic reticular nucleus (TRN) plays an important role in controlling the output of cortically projecting cells in nuclei of the dorsal thalamus has focused attention on the question of whether there exist ascending projections to the TRN from the mesencephalic or other parts of the brainstem reticular formation (BRF). We have examined this and the related question of whether the neurons of TRN project to the BRF, by anterograde and retrograde tracing experiments with horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin. Injections of tracer were placed stereotaxically in the BRF at various depths and rostrocaudal and mediolateral coordinates, and the TRN and adjacent nuclei were examined in serial coronal sections, using tetramethylbenzidine as the principal chromogen. Retrogradely labelled cell bodies were consistently seen in hypothalamus and zona incerta but never in TRN, suggesting that, in the rat, TRN neurons do not project caudal to the thalamus. After 54 out of 60 injections, no terminal label was detected in any part of the TRN although such label was present in other parts of the thalamus, including the intralaminar nuclei, in the same sections. We therefore conclude that direct projections from the BRF to the TRN must be extremely sparse, and that those effects of BRF stimulation upon thalamocortical transmission that are mediated by the TRN (rather than by direct projections to dorsal thalamic nuclei) probably depend chiefly on indirect polysynaptic pathways.

Animals↗

PubMed1986

The effects of prenatal and neonatal monocular enucleation on visual topography in the uncrossed retinal pathway to the rat superior colliculus.

The visual representation in the uncrossed retinal projection to the superior colliculus (SC) was examined electrophysiologically by recording multi-unit responses in paralysed, anaesthetised adult rats (both pigmented and albino), which had been monocularly enucleated either prenatally or soon after birth. This manipulation partially stabilises an exuberant neonatal projection from the remaining eye to the ipsilateral SC. Neuronal responses were also stronger and the multi-unit receptive fields larger than in intact animals. Many of the visual fields recorded on penetrations in caudal SC were located in the peripheral ipsilateral visual hemifield, corresponding to nasal retina. Such receptive fields are not seen in normal animals and were not found in animals enucleated on day 3 or later. The topographic representation of the dorso-ventral retinal axis, lateral to medial in the SC, was normal in all experimental animals. The representation of the naso-temporal retinal axis was abnormal and more variable. In all operated animals as the recording electrode was moved caudally away from the rostral pole of the SC, the corresponding receptive fields moved gradually from up to 40 degrees in the ipsilateral visual hemifield to about 40 degrees into the contralateral hemifield (a location corresponding to the peripheral edge of the temporal retina). This is the mapping polarity found in the normal uncrossed retinal projection. In the enucleated animals, the map was expanded and frequently displayed a clustering of fields arising from far temporal retina. In animals enucleated prenatally or on the day of birth, visual responses could be recorded in more caudal SC. The corresponding receptive fields now moved nasally on the retina, generating reversals in the map. The most caudal penetrations in these early enucleates frequently gave receptive fields located in retina nasal to the optic disc, up to 90 degrees into the ipsilateral visual hemifield. These results demonstrate that a temporal relationship exists between the order and mapping polarity of the visual field in SC and the time of enucleation. Prenatal enucleation produces reversals of the mapping polarity in caudal SC while neonatal enucleation produces an expanded map but one with a mapping polarity appropriate for an uncrossed projection.

Action Potentials↗

PubMed1986

Subcortical afferent and efferent connections of the superior colliculus in the rat and comparisons between albino and pigmented strains.

Subcortical connections of the superior colliculus were investigated in albino and pigmented rats using retrograde and anterograde tracing with horseradish peroxidase (HRP), following unilateral injection of HRP into the superior colliculus. Afferents project bilaterally from the parabigeminal nuclei, the nucleus of the optic tract, the posterior pretectal region, the dorsal part of the lateral posterior-pulvinar complex and the ventral nucleus of the lateral lemniscus; and ipsilaterally from the substantia nigra pars reticulata, the pars lateralis of the ventral lateral geniculate nucleus, the intergeniculate leaflet, the zona incerta, the olivary pretectal nucleus, the nucleus of the posterior commissure, the lateral thalamus, Forel's field H2, and the ventromedial hypothalamus. Collicular efferents terminate ipsilaterally in the anterior, posterior and olivary pretectal nuclei, the nuclei of the optic tract and posterior commissure, the ventrolateral part of the dorsal lateral geniculate nucleus, the pars lateralis of the ventral lateral geniculate nucleus, the intergeniculate leaflet, and the zona incerta; and bilaterally in the parabigeminal nuclei and lateral posterior-pulvinar complex (chiefly its dorsal part). The general topographical patterns of some of the afferent and efferent projections were also determined: the caudal and rostral parts of the parabigeminal nucleus project to the caudal and rostral regions, respectively, of the superior colliculus; caudal superior colliculus projects to the most lateral, and lateral superior colliculus to the most caudal part of the terminal field in the dorsal lateral geniculate nucleus; caudolateral superior colliculus projects to the caudal ventrolateral part of the ventral lateral geniculate nucleus, while rostromedial parts of the colliculus project more rostrally and dorsomedially. Following comparable injections in pigmented and albino animals, fewer retrogradely labelled cells were found in subcortical structures in the albino than in the pigmented rats. The difference was most marked in nuclei contralateral to the injected colliculus. Thus, the effects of albinism on the nervous system may be more widespread than previously thought.

Albinism↗