Heterotopic neocortical transplants. An anatomical and electrophysiological analysis of host projections to occipital cortical grafts placed into sensorimotor cortical lesions made in newborn rats.

Plates of presumptive occipital neocortex obtained from fetal rats at 14-16 days gestation were grafted into the cerebral hemisphere of newborn rats. The transplants were placed heterotopically into sensorimotor cortical lesion cavities made immediately prior to grafting. At maturity, some of the transplants were injected with the retrograde fluorescent tracers Fast Blue and Diamidino yellow. In other animals, single-unit activity in the transplants or in normal cortex was recorded using standard electrophysiological techniques. Histologically, host projections to the transplants were demonstrated by the presence of retrogradely labeled neurons in the host primary and secondary somatosensory cortices as well as several thalamic areas including the anteroventral, anteromedial, ventrobasal, mediodorsal and central medial nuclei. Additional labeling was found in the claustrum, lateral hypothalamus, zona incerta and basal forebrain. Electrophysiologically, transplant single-unit activity was evoked in 43/69 (62%) neurons by thalamic stimulation, but only 1/69 transplant neurons responded to electrical stimulation of the contralateral forepaw. In further work, volumetric measurements showed that the transplants did not ameliorate the thalamic atrophy found after neocortical lesions. These results are compared to previous studies involving the homotopic placement of sensorimotor cortical grafts.     

Transplantation of tectal tissue in rats. II. Distribution of host neurons which project to transplants

Tectal tissue was dissected from fetal rats and transplanted adjacent to the superior colliculus of newborn rats. The recipient animals were then allowed to survive for 6 or more weeks. Subsequent examination revealed that the transplants generally lay over the host inferior colliculus and rostral part of the cerebellum and had substantial fiber connections with the host superior colliculus. To determine which host areas projected to the transplants, horseradish peroxidase (HRP) was injected into the transplants, and the host brain was examined for the presence of retrogradely filled neurons. Labeled cells were found in nearly 50 host areas. Most of these areas are known to project to normal superior colliculus. There was a consistency between one animal and another in the frequency and density of cell label in the various areas. The projection from host cortex (particularly from visual cortical areas) was the densest and most consistent projection. Other areas which commonly projected into the transplants included pretectum, parabigeminal nucleus, superior colliculus, and the brachial region of the inferior colliculus. Sparse and infrequent projections were found from ventral lateral geniculate nucleus, substantia nigra, zona incerta, and catecholaminergic nuclei. No unequivocally labeled retinal ganglion cells were found. The results indicate that the host projection into the transplants is limited to those areas with axons in the vicinity of the host/transplant interconnection. However, the data also suggest that (1) the relative maturity of particular host pathways at the time of transplantation and (2) some form of preferential or absolute affinity expressed between host axons and transplant cells are also factors which influence the pattern of connections formed between host and transplant.     

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.     

Abnormalities in the Development of the Tectal Projection from Transplants of Embryonic Occipital Cortex Placed in the Damaged Occipital Cortex of Newborn Rats

We have examined the degree of precision in the topographic arrangement of the tectal projection developed by homotopic transplants of embryonic occipital cortex and tried to determine whether the development of the corticotectal projection is exclusively dependent on environmental cues or is also controlled by intrinsic factors. Transplants of embryonic (E16) occipital cortex were grafted into various areas of the occipital cortex (Oc1 or Oc2) of newborn rats and the organization of the tectal projection arising from the transplants was subsequently examined by injecting different neurotracers into the transplants. Our results indicate that in most cases the laminar and tangential distributions of the tectal projections from the transplants were abnormal. Indeed, whatever the location of the transplant in the host occipital cortex and whatever the placement of the injection into the transplant, a hybrid distribution of the tectal labeling was found, reminiscent of the pattern observed following tracer deposits in both Oc1 and Oc2 in intact animals. Since the grafts were composed of cells of both Oc1 and Oc2 embryonic origin, it is likely that the hybrid pattern of efferents reflects the heterogeneity of the embryonic origin of the cells composing the graft. These findings provide evidence that the development of the topographic distribution of neocortical efferents is not only dependent on factors extrinsic to the cortex and further indicate that even within one single cortical region, the occipital cortex, different areas (Oc1 vs Oc2) are not totally interchangeable. These findings might have important implications in transplantation experiments aiming at the reconstruction of damaged neocortical circuitry where a precise “point-to-point” reconstruction of the circuitry is expected.     

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats: reciprocal connections with host thalamus demonstrated with WGA-HRP

Fetal frontal cortex was transplanted into lesion cavities formed in host motor/sensory cortex of adult rats. Eight to twenty-eight weeks later wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into host thalamus and the brain was sectioned and reacted using a sensitive TMB procedure. A large amount of fine granular WGA-HRP was detected in most transplants. This could represent anterograde transport demonstrating that injured adult host thalamic neurons sprouted axons into fetal cortical transplants. Conversely, none or very few retrogradely labeled pyramidal neurons were present in the transplants. This indicates that pyramidal neurons in transplants either did not sprout into adult host brain or sprouted such short distances that they did not pick up the WGA-HRP. These results are compatible with the hypothesis that high trophic/growth factor levels in newborn or fetal brain and low levels in adults determine the more extensive connections seen in newborn hosts compared with those in adult transplanted hosts. The data are also consistent with the proposal that adult host brains impair axonal growth. Functionally, the data suggest that although corticofugal effects of fetal cortical transplants in adult host brains are likely to be limited, transplants could exert beneficial trophic effects on adult host thalamic neurons.     

Expression of zinc-positive cells and terminals in fetal neocortical homografts to adult rat depends on lesion type and rearing conditions

Zinc-positive neurons and terminals, known to be associated with the glutamatergic projections in the brain, can be demonstrated by the histochemical Timm method and later modifications thereof. The adult rat neocortex contain a uniform lamination of zinc-positive cells with specific projections to, e.g., the striatum. We have previously reported that fetal neocortical grafts implanted in the adult rat neocortex combined with rearing in an enriched environment can improve behavioral functions and reduce the secondary atrophy of thalamus after cortex infarction in adult rats. In order to examine whether the expression of zinc positivity is ontogenetically inherent to neocortical neurons we grafted fetal neocortical tissue to aspiration or ischemic lesions of the frontoparietal neocortex of adult rats, followed by histochemical visualization of the vesicular zinc pool by selenite or sulfide. One further aim of the study was to elucidate to what extent the distribution of zinc-containing neurons and terminals in the grafts depended on rearing under different environmental conditions. The foremost finding of the present study was that the overall density of zinc-containing terminals in fetal cortical transplants placed in brain infarcts of adult spontaneously hypertensive rats is higher when the rats are reared in an enriched environment. Moreover, the presence and expression of zinc-positive neurons and terminals do not seem to be ontogenetically inherent to the cortical neurons as the fetal neocortical grafts placed in aspiration lesions contained no zinc-selenide-positive neurons and few or no zinc-selenide-positive terminals. The presence or expression of zinc-positive cells may thus be induced by ingrowth of fibers and terminals from the host brain as transplants placed in the ischemic lesions expressed both zinc-positive neurons and terminals.     

Efferent connections of homotopic and heterotopic transplants of embryonic neocortical tissue placed in the occipital neocortex of newborn rats

We examined (i) the capacity of transplants of embryonic neocortex to restore corticofugal systems disrupted following neonatal damage to the occipital cortex and (ii) the influence of the embryonic origin of the transplanted neurons on the reconstruction of the corticofugal circuitry. Transplants of embryonic occipital or frontal cortex were grafted homo- or heterotopically into the damaged occipital cortex of newborn rats. Several months after grafting, an anterograde tracer was injected into each category of transplants. Homotopic transplants developed a set of projections directed exclusively towards most of the cortical and subcortical visual targets normally contacted by occipital cortical neurons. Heterotopic transplants formed a hybrid system of efferent projections that reflected both their embryonic origin and their new location within the host cortex. These findings are consistent with previous results indicating that fetal frontal and occipital neurons are not interchangeable. Consequently, transplantations aiming at the reconstruction of neural circuits disrupted following neonatal damage affecting a given cortical area should only use fetal cortical cells taken from the same cortical locale.     

Replacement of damaged cortical projections by homotypic transplants of entorhinal cortex

The extent to which transplants of embryonic cortical tissue can be used to replace damaged cortical projections has been examined. Embryonic entorhinal cortex was implanted into the entorhinal region of young adult rats that had previously received a lesion through the angular bundle. Projections between transplant and host were examined by using WGA-HRP and the fluorescent dye Fast Blue. Implants selectively innervated areas of the host hippocampus and amygdala which normally receive entorhinal afferents. Implants were innervated by cells in the host diagonal band and, in one case, by cells in the contralateral entorhinal and/or presubicular cortex. In most cases, host fibers were differentially distributed within transplants, possibly reflecting an ability of host fibers to recognize and selectively innervate their appropriate targets even though the cellular organization of the implant is different from that present during normal development. These data suggest that homotypic implants of embryonic entorhinal cortex can, in some ways, replace severed cortical projections and may eventually be able to reconstitute normal cortical circuitry.     

Neocortical Grafts Placed in the Infarcted Brain of Adult Rats: Few or No Efferent Fibers Grow from Transplant to Host

The present stud y examines the capacity of fetal neocortical grafts placed in a brain infarct to exchange axonal projections with the host brain. Five to 7 days after a middle cerebral artery occlusion in adult spontaneously hypertensive rats, dissociated neocortical primordium from fetuses of gestational age 15-16 days was implanted into the infarcted area. Four to 11 months later, the neural tracers Phaseolus vulgaris-leucoagglutinin and Fluoro-Gold were injected in the grafts and host neocortex. An extensive axonal network was present in the transplants but only one of eight rats with appropriate placed injections displayed efferent connections from transplant to host. The sparse axonal outgrowth indicates major limitations for fetal rat cortical grafts to form connections with host neural circuitries after an ischemic insult.     

Fetal Neocortical Tissue Blocks Implanted in Brain Infarcts of Adult Rats Interconnect with the Host Brain

The purpose of the present study was to study if the connectivity of fetal neocortical tissue blocks placed in ischemic brain infarcts of adult rats would be enhanced in rats housed in an enriched environment. We also investigated whether the enriched housing conditions could enhance the postischemic and postgrafting functional outcome, in terms of motor behavior. This part of the study has been published recently. The middle cerebral artery was ligated on the right side in 37 inbred, adult male spontaneously hypertensive rats. The rats were placed at random either in an enriched environment (groups A and B) or in standard laboratory cages (group C). Three weeks after the artery occlusion, blocks of fetal sensorimotor cortex (Embryonic Day 17) were transplanted into the infarct cavity of rats from groups B and C. After 9 weeks all transplanted rats received an injection, into the graft, of a mixture containing the two tracers Fluoro-Gold and biotinylated Dextran amine. The transplants revealed a structured morphology with whorls and bands of cells reminiscent of normal neocortex. Tracing of efferent transplant to host fibers with biotinylated Dextran amine showed pronounced intrinsic transplant projections, as well as fibers, although significantly fewer, to the host ipsilateral sensorimotor cortex, striatum, and thalamus. Host to transplant projections were revealed by Fluoro-Gold-labeled cells found in the ipsilateral host sensorimotor cortex, the basal nucleus of Meynert, the thalamic ventrobasal, ventrolateral and posterior nuclei, and in the dorsal raphe nuclei. We conclude that fetal frontal neocortical block grafts placed in brain infarcts of adult rats develop a morphology reminiscent of normal neocortex and that both afferent and efferent neural connections, although sparse, are established with the host brain, whether the rats are reared under enriched housing conditions or not.     

Organization of cerebral cortical afferent systems in the rat. II. Hypothalamocortical projections

The organization of hypothalamic projections to the cerebral cortex in the rat has been studied using retrograde and anterograde tracer methods. Four separate populations of hypothalamic neurons, which constitute a major source of diffuse cortical innervation, were identified: Tuberal lateral hypothalamic (LHAt) neurons which innervate the cerebral cortex tend to cluster in the perifornical region, in the zona incerta, and along the medial edge of the cerebral peduncle, at levels roughly coextensive with the ventromedial hypothalamic nucleus. Most of these neurons project to the ipsilateral cortex; a small percentage innervate the contralateral cortex, but this varies among cortical terminal fields. The perifornical neurons are organized in a roughly topographic medial-to-lateral relationship with respect to their cortical terminal fields. Field of Forel (FF) neurons, which project primarily to the frontal cortex of the ipsilateral hemisphere, are located just ventral to the medial edge of the medial lemniscus, at the level of the ventromedial basal thalamic nucleus. The more laterally placed neurons innervate the lateral frontal, insular and perirhinal cortex; the more medial neurons, around the mammillothalamic tract, innervate the medial frontopolar, prelimbic, infralimbic, and anterior cingulate cortex. Posterior lateral hypothalamic (LHAp) neurons form a dense cluster spanning the lateral hypothalamus, from the cerebral peduncle to the posterior hypothalamic area at premammillary levels, and extending into the supramammillary nucleus and the adjacent ventral tegmental area. LHAp neurons innervate the entire cerebral cortex, predominantly on the ipsilateral side. Populations of LHAp neurons projecting to different cortical target areas show considerable spatial overlap, but computer plots of the centers of these populations demonstrate a strict topographic relationship with respect to the cerebral cortex. Tuberomammillary (TMN) neurons form a sheet along the ventrolateral surface of the premammillary hypothalamus. About twice as many TMN neurons innervate the ipsilateral, as compared to the contralateral hemisphere; it is not known whether single neurons project to both hemispheres. No topographic organization of the TMN cortical projection is apparent. Injections of different-colored fluorescent dyes into various cortical areas demonstrate that hypothalamic neurons in general have rather restricted cortical terminal fields. Only occasional neurons are found, primarily in LHAt, which are double labeled by injections into different cytoarchitectonic areas.(ABSTRACT TRUNCATED AT 400 WORDS)     

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-;menth-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 of 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.     

Organization of visual cortical projections to fetal tectal transplants in rats: a study using multiple retrograde tracers

Retrograde tracing techniques have been used to study the host visual cortical projection to fetal tectal tissue grafted to the midbrain of newborn host rats. To determine whether there is any topographic order in these cortical afferents, different parts of the grafts were injected with 3 different tracers: Fast blue (FB), Diamidino yellow dihydrochloride (DY), and either horseradish peroxidase (HRP) or rhodamine-labelled microspheres (Rh). The comparative visual cortical distribution of cells retrogradely labelled with the different dyes was then examined. Tectal tissue from 15-day-old pigmented rat embryos was injected via a glass micropipette onto the dorsal midbrain of anaesthetised newborn rats of the same strain. In adulthood, host rats were examined for the presence of grafts; 21 grafts were injected with retrograde tracers and the cortices of 12 of these animals were mapped to show the relative location of FB-, DY-, HRP- or Rh-labelled cells. Qualitative inspection of area 17 did not reveal consistent evidence of point-to-point visuotopic mapping in the cortico-transplant projection. However, within area 17 statistical analysis (chi 2 tests) revealed significant differences in most brains in the relative distribution of FB-, DY-, HRP- or Rh-labelled neurons. Areas 18 and 18a contained greater numbers of retrogradely labelled cells. In these extrastriate regions, statistical analysis also indicated significant differences in the relative distribution of neurons labelled with different tracers. These data thus provide evidence for a non-random pattern of cortical innervation of tectal grafts. Possible reasons for the absence of coherent, topographically organized cortico-transplant maps typical of the normal corticotectal projection are considered.     

Transplantation of embryonic occipital cortex to the brain of newborn rats: a Golgi study of mature and developing transplants

Segments of the occipital cortex were taken from rat embryos (E16-E19) and transplanted to the cerebral cortex or the tectal region of a newborn rat host. With the aid of Golgi impregnation techniques, neuron morphology was studied in cortical transplants which had survived for 1 week or more in the host brain. In mature transplants (greater than 4 weeks) three main groups of neurons, termed groups I-III, were identified. Group I neurons resembled pyramidal neurons of the intact cerebral cortex. No preferential orientation of either soma or dendrites of group I neurons was observed in the transplants, and some group I neurons had curved apical dendrites. Group II neurons had predominantly stellate form and their dendrites were densely covered with spines. Paucity or absence of dendritic spines characterized group III neurons which exhibited various dendritic topologies. Different neuron types were also recognized in immature transplants growing for 1 and 2 weeks in the host brain. The sequence of dendritic maturation of transplanted cortical neurons is similar to that seen in intact cortex, although the stage reached related more to the actual age of the transplant than to that of the host. Thus, group I neurons in the 1-week-old transplants taken from E16 embryos had not attained the same complexity of branching as pyramidal neurons in the surrounding host cortex, but rather resembled slightly younger cells more like those found in the cerebral cortex of the newborn rat. These results show, therefore, that at least the basic cell classes identified in intact visual cortex can also be recognized in the cortical transplants. This will provide a foundation for studies defining which cells project to the host brain and which are involved in particular intrinsic connections.     

Retrograde transport of fluorescent tracers reveals extensive ipsi- and contralateral claustrocortical connections in the rat

The projections from the claustrum to the cerebral cortex in the rat were examined by means of retrogradely transported fluorescent tracers Fast Blue (FB) and Diamidino Yellow dihydrochloride (DY), injected in the prefrontal, motor, somatosensory, auditory, and visual fields. In all cases, substantial numbers of retrogradely labeled neurons were observed in the ipsilateral and moderate to scant numbers in the contralateral claustrum insulare. Symmetrical bilateral injections of FB and DY as well as simultaneous injections of the tracers in the motor and visual cortex of the same hemisphere revealed no double-labeled neurons in the claustrum. The following conclusions may be drawn: The claustral projections to the motor, somatosensory, and visual cortex are prominent. The projection to the prefrontal cortex is less substantial and that to the auditory cortex is relatively modest. The claustrocortical connections lack the clear-cut topographic pattern of the thalamic nuclei but are, to some degree, preferentially arranged, albeit with considerable overlapping of the subpopulations of corticopetal neurons, a coarse anteroposterior topographic distribution appears to exist also in rodents. Neurons contributing to the claustrocortical connection project either ipsilaterally or contralaterally but not bilaterally. Projections to different cortical fields of one hemisphere also originate from separate claustral neurons.     

Thalamic projections to sensorimotor cortex in the newborn macaque.

In the present experiments thalamocortical projections to different functional areas of the newborn (or prematurely delivered) macaque's sensorimotor cortex were labeled using retrogradely transported fluorescent dyes. Several dyes were used in each animal to (1) enable the direct comparison of the soma distributions of different thalamocortical projections within thalamic space, and (2) identify by double labeling neurons shared between these distributions. The projection patterns in the newborn macaque were compared with those of the mature animal reported by Darian-Smith et al. (J. Comp. Neurol. 1990;298:000-000). The main observations were (1) all thalamocortical projections to the sensorimotor cortex of the mature macaque are well established by embryonic days 146-150, as was shown by labeling these pathways in infants delivered by cesarean section, (2) a significant number of thalamocortical neurons in the newborn were double-labeled following dye injections into different pre- or postcentral areas, and where the margins of the dye uptake zones were separated by 3-8 mm, and (3) extensive projections from the anterior pulvinar nucleus to the motor and premotor cortex, and to the supplementary motor cortex were labeled in the newborn macaque. Both the exuberant terminal arborizations, and the precentral pulvinar projections were diminished by the 6th postnatal month, and absent in the mature macaque. The role of epigenetic determinants of these postnatal events is briefly considered.     

Electrophysiologic research on the afferent connections of embryonic neocortex allografts inserted into the projection zones of the cortex in adult rats

Grafts of the rat fetal neocortex (the 17th-18th day of gestation) were placed into the cavity made by aspiration in the primary visual or somatosensory cortex of adult rats. Electrophysiological studies performed 3-3.5 months later showed that approximately in 50% of animals the neurons of the transplants responded to sensory stimuli of modality specific for cortical regions replaced by the transplant. These responses were elicited from local receptive fields that in some animals revealed topographic organization. Neuronal responses of transplants were elicited by local electrical stimulation of thalamic nucleus projecting to the cortical site of grafting, as by stimulation of contralateral homotopic cortical areas. Latency and temporal patterns of neuronal responses were similar to normal ones. Thus it may be concluded that afferent inputs to the cortical transplants retrace normal cortical inputs. The possible mechanisms of re-innervation of the grafts are discussed.     

Transplantation of fetal postmitotic neurons to rat cortex: survival, early pathway choices and long-term projections of outgrowing axons

A system for studying growth and development of transplanted subpopulations of postmitotic cerebral cortical neurons is described. The cytotoxic drug methylazoxymethanol (MAM) was given to pregnant rats on the fourteenth day of gestation to destroy precursor cells of layers II-IV of the fetal cerebral cortex. Layer V and VI precursor cells which had completed their final division before MAM treatment and were unaffected by it, were labeled by a prior injection of [3H]thymidine. This strategy provides a donor cerebral cortex containing mainly neurons destined to form layers V and VI of the adult cerebral cortex; these cells are postmitotic. Pieces of donor cerebral cortex were transplanted to the cerebral hemispheres of normal newborn hosts at one day, two days, or 6 days after MAM treatment; survival was assessed 1-12 weeks after transplantation by autoradiography of histological sections. Radiolabeled graft cells survived in 89% of recipients and many of these grew axons into the host, as indicated by retrograde labeling with horseradish peroxidase. Significant numbers of graft cells could also be stained immunocytochemically for glutamic acid decarboxylase or for the peptides, somatostatin, vasoactive intestinal polypeptide or cholecystokinin. A second group of experiments examined the routes of early axon outgrowth from normal and postmitotic fetal grafts. When the donor cortex had been incubated in a mixture of [3H]proline and [3H]leucine for 20 min prior to transplantation, the earliest axons growing out of the graft into normal newborn hosts could be assessed by autoradiography of axoplasmic transport after survivals in the host of 7 days. Normal and postmitotic grafts taken at E15 or E20 were capable of outgrowth, though the axons of E20 postmitotic cells did not grow far. The location of the transplant was the major determinant of where graft cells' axons grew and growth was mainly into existing axonal pathways of the host. In a third group of experiments, long term axonal projections from normal and postmitotic fetal transplants to 4 regions of the host brain--thalamus, contralateral cortex, striatum, and hippocampus--were examined with retrograde tracers 2-4 months after transplantation. Projections from grafts to the 4 host sites were highly dependent on the presence of nearby host axons connecting with those sites. Neurons in all types of graft projected to one or other of the 4 sites, but generally in small numbers. Higher proportions of cells in grafts from E15 MAM-treated donors projected to the host thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death

Rubrospinal tract cells undergo massive retrograde degeneration following spinal cord damage in newborn rats (Prendergast and Stelzner, J. Comp. Neurol. 166:163-172, '76b). In the current study, fetal spinal cord tissue (E12-14) was grafted into midthoracic spinal cord lesions in newborn rats (less than 72 hours old) in order to determine whether such transplants could modify the response of the immature host central nervous system (CNS) to axotomy. These transplants grew, differentiated, and formed extensive areas of apposition with the recipient spinal cords. Counts of red nucleus (RN) neurons indicated a significant loss of RN neurons in animals with lesion alone, but a rescuing of most of these cells if a transplant was placed into the lesion site. In fact, the number of neurons in animals with lesions and transplants was not significantly different from control animals. Horseradish peroxidase injected 10-15 mm caudal to the transplant (at 1-12 months post-transplantation) labeled neurons within the transplant and RN neurons contralateral to the spinal cord lesions and transplant. In animals with spinal cord lesion but no transplant, only the unaxotomized RN was labeled. Thus, spinal cord transplants prevented the massive retrograde cell death of immature axotomized rubrospinal neurons. Some of these rescued neurons projected to the host spinal cord caudal to the transplant.     

Selective elimination of axons extended by developing cortical neurons is dependent on regional locale: experiments utilizing fetal cortical transplants

In adult rats, cortical neurons that extend an exon through the pyramidal tract (a major subcortical efferent projection of the neocortex) are limited to layer V of about the rostral two-thirds of the neocortex. In neonates, however, pyramidal tract neurons are distributed throughout the neocortex, but all of those found in certain areas, such as the posterior occipital region (including primary visual cortex) selectively lose their pyramidal tract axon (Stanfield et al., 1982) yet maintain axon collaterals to other subcortical targets (O'Leary and Stanfield, 1985). To determine if the regional location of a developing pyramidal tract neuron critically influences the maintenance or elimination of the axon collaterals it initially extends, pieces of cortex from embryonic day 17 (E17) rat fetuses (exposed to 3H-thymidine on E15) were transplanted heterotopically into the cortex of newborn (PO) rats; rostral cortex was placed into the posterior occipital region (R----O), or posterior occipital cortex into a rostral cortical locale (O----R). The retrograde tracers Fast blue (FB) and Diamidino yellow (DY) were used to assay for the presence of specific populations of cortical projection neurons within the autoradiographically identified transplants. In terms of the extension and maintenance of pyramidal tract axons, the transplanted neurons behave like the host neurons of the recipient cortical region rather than like those of their site of origin. At P40, following FB injections into the pyramidal decussation on P34, pyramidal tract neurons are labeled within the O----R transplants, but none can be labeled within R----O transplants, although in the same R----O cases transplanted neurons are labeled by an injection of DY in the superior colliculus. However, at P13 pyramidal tract neurons can be identified within the R----O transplants, as well as in the host occipital cortex, following injections made on P9, a period when the distribution of pyramidal tract neurons in normal rats is widespread (Stanfield and O'Leary, 1985b). In a second series of host rats, on P34 FB was injected in the pyramidal decussation of the O----R cases, or in the superior colliculus of the R----O cases, and in both groups DY was injected into the region of contralateral cortex homotopic for the new location of the transplant. On P40, in both the O----R and R----O transplants, many neurons singly labeled with FB or DY are found, but no double dye-labeled cells are seen.(ABSTRACT TRUNCATED AT 400 WORDS)