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R D Lund

Publications and source records attributed to R D Lund.

At least 127 records · Page 7Linked to original sources

Tectal transplants into the occipital cortex of the newborn rat.

Embryonic day 15 rostral tectum (presumptive superior colliculus) was transplanted into the occipital cortex of newborn rats. One to two months later, the transplants were visualized and injected with either horseradish peroxidase (HRP) or wheat germ agglutinin conjugated with HRP (WGA/HRP). After the appropriate survival time and processing with either diaminobenzidine (DAB) or tetramethylbenzidine tetrahydrochloride (TMB), HRP-labelled pyramidal cells were found in layer V of the host ipsilateral occipital cortex. Thus, the occipitotectal connections are formed between host and graft despite the fact that the fibers must grow in a direction opposite to their normal course to reach the aberrantly positioned tectal graft.

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Amphetamine- and stress-induced turning after nigral transplants in neonatally dopamine-depleted rats.

Neonatally dopamine-depleted rats fail to show the deficits seen in similarly lesioned adults, and no longer appear to require dopamine. Nevertheless, unilateral nigral transplants provided extensive reinnervation and were capable of modifying motor patterns. Both amphetamine and external stressors elicited contraversive turning. This raises the question of whether extrinsic dopamine innervation supplements or overrides alternative compensatory mechanisms in the neonate.

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Target regions enhance the outgrowth and survival of ganglion cells in embryonic retina transplanted to cerebral cortex in neonatal rats.

In embryonic mouse retina transplanted to occipital cortex of neonatal rats, ganglion cells do not project axons into the host cortex, although they may survive up to but not beyond 6 weeks post-transplantation. By contrast, if embryonic tectum or diencephalon is transplanted along with the retina, ganglion cells exhibit vigorous outgrowth to specific regions of the co-transplant and are able to survive for at least 14 weeks.

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Retinal transplants can drive a pupillary reflex in host rat brains.

Retinae taken from embryonic rats were transplanted over the midbrain of neonatal rats, from whom one eye had been removed. After 5 months, the optic nerve of the remaining eye was cut, and the transplant was exposed. Illumination of the transplant caused pupilloconstriction of the host eye, a response abolished by damaging the transplant. Thus neural transplants are capable of driving specific reflexes in response to natural stimuli.

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Cell surface changes in the developing optic nerve of mice.

A recently defined antibody to a cell surface protein, M6, inhibits neurite outgrowth in culture (Lagenaur, Fushiki, and Schachner: Soc. Neurosci. Abstr. 10:739, '84). In the developing mouse, the antibody stains all parts of the primary optic pathway at birth. Over the next week, staining is lost from the proximal segment of the optic nerve and a week later from the more central part of the nerve. By contrast staining persists through adulthood in the optic fiber layer of the retina. This means that single axons in the mature optic nerve express the antigen over only the proximal few millimeters of their course and over their terminal region. The results are discussed in relation to the overall maturation of the optic pathway and to the processes of membrane maturation and myelination.

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Sprouting of serotoninergic afferents into striatum after dopamine-depleting lesions in infant rats: a retrograde transport and immunocytochemical study.

Intraventricular injections of 6-hydroxydopamine in 3-day-old rats resulted in the near-total loss of tyrosine-hydroxylase-immunoreactive processes in the striatum when examined 2-6 months later. This destruction of dopamine (DA) afferents was accompanied by an increase in the density of serotonin (5-HT)-immunoreactive fibers in the striatum. The hyperinnervation was most striking in the rostral striatum, an area containing few 5-HT-immunoreactive fibers in control rats. Retrograde tracing, with either horse-radish peroxidase or rhodamine-labelled microspheres, indicated a significant increase in the number of neurons projecting to the rostral striatum from the dorsal raphe nucleus of lesioned animals. The increase was largely confined to the rostral extent of the dorsal raphe, and overlapped the distribution of cells labelled after injections of HRP into caudal striatum of control and lesioned animals. In sections additionally processed for immunocytochemistry, 80-90% of retrogradely labelled raphe neurons in both groups of animals were found to be 5-HT-immunoreactive. None of changes encountered in infant-lesioned rats were observed 2-4 weeks after 6-HDA was given to adult animals. These findings demonstrate that removal of DA afferents during development leads to an enlargement of the serotoninergic projection from the raphe nucleus to the striatum.

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The lamination and connectivity of embryonic cerebral cortex transplanted into newborn rat cortex.

Sheets of frontal or occipital cerebral cortex were taken from embryonic day (E) 15 rat embryos and placed in shallow depressions made in the occipitoparietal region of newborn rats. These transplants developed normal patterns of lamination, which could be in an inverted orientation if the transplant itself was placed upside down. Irrespective of the cortical area of origin of the grafted tissue, the transplants consistently received projections from those host thalamic nuclei that were normally found to innervate the adjacent host cortex. This indicates that immature cortical tissue, up to at least E15, may not contain the information necessary to define the specific thalamocortical connections characteristic of individual areas. On the contrary, the observed input pattern may be the result of sprouting of fibers that normally innervated host cortical regions adjacent to the transplant. Similarly, callosal afferents to transplants seemed to be a direct extension of the callosal input to the host cortex immediately beneath the transplant. Results from HRP studies of callosal connections indicated that transplant efferents to the contralateral cortex are smaller in magnitude than their afferents. This may be related to the superficial location of the transplants, which may limit the access transplant efferents have to the white matter. This study suggests that, while the cortical lamination is largely determined intrinsically, the innervation of the cortex is influenced by the context in which it develops.

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Maintenance of transient occipitospinal axons in the rat.

A developmentally transient occipitospinal projection arising from the visual association cortex persists if a fetal tectum is transplanted to the spinal cord at birth and at the same time, the host tectum is removed. The pathway is not sustained if the transplant is placed in the cord without a tectal lesion or if the tectum alone is damaged. Thus the tectal transplant promotes the survival of normally transient occipitospinal axons as long as another regular target of these axons is removed.

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Use of a species-specific antibody for demonstrating mouse neurons transplanted to rat brains.

A cell surface monoclonal antibody specific for mouse central nervous system neurons was used to identify mouse tissue transplanted to neonatal rat brains. Neuronal cell bodies and processes were stained in the transplants. Immature axons were stained growing out of the transplants into the host brain; and in mature brains unmyelinated axons and terminal plexuses were demonstrated. The technique allows a variety of studies to be performed on transplant-host interactions, especially in circumstances where the two are closely apposed.

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Ganglion cells in retinae transplanted to newborn rats.

Cells projecting out of retinal transplants placed over the tectum of newborn rats were studied by labelling with horseradish peroxidase 1 month or more after transplantation. Using this technique, it was found that only cells with the dendritic characteristics of ganglion cells were labelled and, furthermore, that the major classes of ganglion cells seen in normal retinae were also present in the transplants. The cell body size histograms of ganglion cells in normal and transplanted retinae compared closely with each other. Dendritic trees were closely confined by the limits of the inner plexiform layer, and if that layer was folded or distorted, they were themselves frequently abnormal. While axons usually coursed over the surface of the retinal transplants, they quite often followed an anomalous course crossing the individual layers. It appears, therefore, that this transplantation procedure has relatively little impact on the ability of ganglion cells to develop many of their characteristic morphological features. Whether the different functional responses of the various ganglion cell classes are also preserved after transplantation is a matter for further investigation.

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The development of callosal projections in normal and one-eyed rats.

The course of callosal development in area 17 of rats suggests that, unlike immediately adjacent regions, axons of callosal origin do not normally gain access to upper cortical layers, and this results in the loss of an early exuberant callosal pathway. Removal of optic input, however, permits invasion of these layers of area 17 by callosal axons and results in survival of callosally projecting neurons in area 17.

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Transplantation of tectal tissue in rats. IV. Maturation of transplants and development of host retinal projection.

We have examined the time course of maturation of embryonic tectal tissue transplanted to the midbrain region of newborn rats and studied the development of the host retinal projection to the grafts. Transplants were examined 2-19 days after transplantation. The morphology of developing transplants was studied using Holmes silver and neutral red stained material. Tectal transplants attained their mature morphology about 17 days after transplantation. The time course of tectal transplant maturation appeared to be similar to that of normal superior colliculus in situ. The development of the host retinal projection into the transplants was examined by injecting the host eyes with horseradish peroxidase (HRP) at various times after transplantation. Retinal fibers anterogradely labeled with HRP were first seen growing into the transplants 3-4 days after transplantation. Ingrowing fibers were always located close to the surface of the transplants. The rate of growth of optic axons into the grafts was estimated to be about 250 to 300 micron per day. Patch-like arborizations of retinal afferents were formed soon after innervation and the mature pattern of optic innervation was established by about two weeks. There was no evidence for an initial transitory phase in which the axons invaded the whole transplant. The development of the host retinal projection preceded morphological maturation of the transplants. The mode of ingrowth of retinal axons into tectal grafts was in many respects similar to the way optic fibers grow into the superior colliculus during normal in situ development. The transplant technique thus provides an opportunity to manipulate and analyze the factors which guide optic fiber growth in intact brains.

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Loss of ganglion cells in fetal retina transplanted to rat cortex.

Fetal retina survived and differentiated when placed into the cortex of newborn host rats. Two months after transplantation, anterograde tract tracing techniques failed to reveal any projections from these transplants into the host brain. Soma-size analysis of the cells in the ganglion cell layer of the transplants suggested that only displaced amacrine cells remained and that the ganglion cells had degenerated. The basis for these results is considered relative to trophic maintenance of ganglion cells, retinal axon guidance, and specificity of connections.

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Development of fetal retina, tectum, and cortex transplanted to the superior colliculus of adult rats.

Earlier studies showed that embryonic retina, cortex, or tectum transplanted adjacent to the superior colliculus of newborn host rats differentiated many of the histological features appropriate for the donor region and developed interconnections with the host nervous system. In the study presented here, the same regions were transplanted to the brain of adult host rats and the development of these transplants was compared to those into newborn hosts. Retina, rostral tectum, or occipital cortex was dissected from donor rat embryos on gestational day 14 or 15. A portion of cortex was aspirated in 2-month-old host rats to expose the right superior colliculus, and one of the donor tissues was placed adjacent to the colliculus in each host. Two to 4 months after transplantation, transplant histology and neuronal interconnections between the transplant and host nervous system were studied by using Nissl and neurofibrillar stains and 3H-proline and HRP tract tracing techniques. Four main points can be drawn from these results. First, 80% of the transplants survived in adult hosts - a percentage comparable to that found in newborn hosts. Second, each of the types of tissues transplanted differentiated histological characteristics appropriate for its site or origin, although the degree of differentiation was always much less than in transplants to newborns. Third, the transplants developed only relatively local projections into the host cortex and superior colliculus. This contrasts with the extensive projections found from the transplants into the brain of newborn hosts. Fourth, no definitive projections from the host retina or brain were identified to any of the transplants into adults, whereas both cortical and tectal transplants into newborns received projections from the host.

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