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Biomedical subjects

G Jeffery

Publications and source records attributed to G Jeffery.

At least 55 records · Page 3Linked to original sources

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↗

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)

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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)

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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.

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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.

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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.

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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.

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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↗

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.

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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↗

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↗

The relationship between cell density and the nasotemporal division in the rat retina.

Cell counts in the ganglion cell layer of the rat retina have been undertaken following unilateral injections of horseradish peroxidase into the ipsilateral thalamus. By retrograde transport, the tracer defined the location of the uncrossed retinal projection, making it possible to determine the relationship between the area of highest cell density and the nasotemporal division. Here it is demonstrated that unlike in the primate and cat, these two regions of retinal specialisation reside in different locations, with the nasotemporal division displaced temporally to the area of highest cell density.

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Early unilateral eye removal produces a regional gradient in soma sizes in the uncrossed projection from the remaining eye.

Early unilateral eye removal reduces natural cell death within the population of ipsilaterally projecting ganglion cells in the remaining eye. Here it is shown that there is a gradient in the soma sizes of cells which survive as a consequence of this manipulation. The additional ipsilateral projection from the far temporal retina arises mainly from cells with medium-to-large somas. Those located on the nasal side of the optic disk have small somas, while those located between the optic disk and the naso-temporal division arise from predominantly small cells whose soma sizes are intermediate between those which are located in the more nasal and more temporal regions.

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Does the early exuberant retinal projection to the superior colliculus in the neonatal rat develop synaptic connections?

The retinal projections of newborn rats are more extensive than those of the adult and retract to form the adult pattern during the first week after birth. In this study, the retinal projections from one eye of newborn hooded rats were labeled by anterograde transport of horseradish peroxidase (HRP) following intravitreal injection of the tracer, and HRP-labeled axons and terminals were then sought by electron microscopy in coronal sections of the superior colliculus cut at 3 levels: rostral, middle and caudal. Labeled presynaptic profiles were present in the superior colliculus on the side contralateral to the injection at all rostro-caudal levels and in the rostral portion of the ipsilateral superior colliculus. But in approximately 37 sections analyzed in detail from 11 animals, only one example was found of an unequivocally presynaptic profile in the middle or caudal regions of the ipsilateral superior colliculus. Thus it would appear that in the newborn hooded rat, the exuberant ipsilateral projections to the middle and caudal parts of the superior colliculus form no or very few transient synaptic connections.

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Retinal ganglion cell death and terminal field retraction in the developing rodent visual system.

The anterograde and retrograde transport of HRP has been employed in neonatal rats and adult rats which were unilaterally enucleated at various stages during the first week after birth. In neonatal animals given unilateral thalamic implants of horseradish peroxidase, the number of labelled retinal ganglion cells in the ipsilateral eye declines over the first week. This is considered to be a consequence of cell death. At the same time unilateral intraocular injections of the same tracer reveals that the terminal field of ipsilaterally projecting retinal axons in the dorsal lateral geniculate nucleus is retracting to form the adult pattern. It is proposed that retraction and ganglion cell death are related. In the monocular adult animals it is shown that fewer ipsilaterally projecting ganglion cells are found the later enucleation takes place. But the number of ipsilaterally projecting cells found in the adult animal enucleated at birth is not as great as the number found in the newborn rat. In spite of this the proportion of the dorsal lateral geniculate nucleus occupied by ipsilaterally projecting ganglion cells is similar in neonates of a given age and adults that were enucleated at that age.

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Transneuronal effects of early eye removal on geniculo-cortical projection cells.

Iontophoretic injections of horseradish peroxidase (HRP) were made into the primary visual cortex of normal rats, and into the visual cortex ipsilateral to the remaining eye of neonatally enucleated rats. The distribution of retrogradely labelled cells in the dorsal lateral geniculate nucleus (LGNd) in the two groups was compared. In normal animals labelled cells were found running in a discrete column through LGNd following the relevant line of projection. In enucleated animals the cells were less tightly grouped through the structure, although the lines of projection coursed in the same general direction. These results suggest that the consequences of early monocular enucleation upon the retinal projection from the remaining eye are transmitted beyond the regions receiving direct input from the eye to secondary visual projections.

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Crossed and uncrossed visual topography in dorsal lateral geniculate nucleus of the pigmented rat.

1. The representation of the retinocentric visual field within the dorsal lateral geniculate nucleus (dLGN) was assessed electrophysiologically by recording multicellular responses from anesthetized pigmented rats. Separate experiments examined the representation through either the contralateral or ipsilateral eye along the dorsoventral, mediolateral, and rostrocaudal dimensions of the nucleus. 2. The crossed projection displays an orderly representation of the visual field, mapping eccentricities out to 100 degrees from the optic disk. There is, however, a marked absence of eccentricities greater than 60 degrees representing upper nasal visual space. The uncrossed projection also displays an orderly representation of the visual field but is limited in extent to upper nasal visual space at far eccentricities of 50-90 degrees. 3. The ipsilateral projection, which represents far eccentric upper nasal visual space, occupies a region in the contralateral representation corresponding with upper nasal visual space at reduced eccentricity. It is these two regions that are considered binocularly conjugate: the temporal crescent of each eye with another crescent (the conjugate central crescent) lying between the optic disk and the temporal crescent of the opposite eye. It is suggested that the crossed and uncrossed representations are aligned in the dLGN so that projection lines for discrete regions of the binocular visual field course through the nucleus from rostroventral to caudodorsal. Although the dLGN of the rat lacks the cytoarchitecturally distinct laminae associated with the regions of afferent input from each eye, as is seen in the primate and cat dLGN, the organizing principle of apposing the representation of the visual field through each eye is similar.

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