Thalamic development induced by Shh in the chick embryo.

Patterning of the early neural tube is achieved in part by the inductive signals, which arise from neuroepithelial signaling centers. The zona limitans intrathalamica (ZLI) is a neuroepithelial domain in the alar plate of the diencephalon which separates the prethalamus from the thalamus. The ZLI has recently been considered to be a possible secondary organizer, effecting its inductions via sonic hedgehog (Shh), a signaling molecule which drives morphogenetic information for the thalamus. Using experimental embryological techniques involving the generation of chimeric embryos, we show that the formation of the ZLI in the diencephalic alar plate is due to an interaction between the prechordal and epichordal plate neuroepithelia. We also provide evidence that Shh expression in the ZLI underlies the morphogenetic activity of this putative diencephalic organizer. Ectopic Shh led to the auto-induction of its own gene expression in host cells, as well as to the expression of other genes involved in diencephalic regionalization and histogenesis. Analysis of long-term surviving embryos after Shh ectopic expression demonstrated that Shh was able to induce thalamic structures and local overgrowth. Overall, these results indicate that Shh expressed in the ZLI plays an important role in diencephalic growth and in the development of the thalamus.

Upregulation of activating transcription factor 3 (ATF3) by intrinsic CNS neurons regenerating axons into peripheral nerve grafts.

The expression of the transcription factor ATF3 in the brain was examined by immunohistochemistry during axonal regeneration induced by the implantation of pieces of peripheral nerve into the thalamus of adult rats. After 3 days, ATF3 immunoreactivity was present in many cells within approximately 500 mum of the graft. In addition, ATF3-positive cell nuclei were found in the thalamic reticular nucleus (TRN) and medial geniculate nuclear complex (MGN), from which most regenerating axons originate. CNS cells with ATF3-positive nuclei were predominantly neurons and did not show signs of apoptosis. The number of ATF3-positive cells had declined by 7 days and further by 1 month after grafting when most ATF3-positive cells were found in the TRN and MGN. 14 days or more after grafting, some ATF3-positive nuclei were distorted and may have been apoptotic. In some experiments of 1 month duration, neurons which had regenerated axons to the distal ends of grafts were retrogradely labeled with DiAsp. ATF3-positive neurons in these animals were located in regions of the TRN and MGN containing retrogradely labeled neurons and the great majority were also labeled with DiAsp. SCG10 and c-Jun were found in neurons in the same regions as retrogradely labeled and ATF3-positive cells. Thus, ATF3 is transiently upregulated by injured CNS neurons, but prolonged expression is part of the pattern of gene expression associated with axonal regeneration. The co-expression of ATF3 with c-jun suggests that interactions between these transcription factors may be important for controlling the program of gene expression necessary for regeneration.

Early (E12) cortical progenitors can change their fate upon heterotopic transplantation.

To help understand how the cortical map is set up during the early stages of corticogenesis, we have examined the developmental fate of embryonic day (E) 12 cortical progenitors in the rat. We have analysed the pattern of thalamic connections and cytoarchitectonic organization developed by progenitor cells removed at E12 from the presumptive parietal or occipital cortex and grafted into the parietal cortex of newborn hosts. Occipital progenitors grafted into the parietal cortex differentiated into neurons that developed reciprocal connections with the ventrobasal complex of the host thalamus. They could also form barrel-like structures, within which axons of the ventrobasal complex were distributed in dense patches. Some of these barrel-like structures were arranged in rows. Moreover, these progenitors failed to develop characteristic traits of occipital cortex cells as they did not establish connections with the dorsal lateral geniculate nucleus. We propose that cortical progenitors are not committed at E12 and, upon heterotopic transplantation, have the capacity to respond to local cues and to subsequently differentiate and maintain major phenotypic characteristics of neurons in their new environment. Only early progenitors are multipotent. By E13/E14, indeed, most cortical cells become irreversibly committed and upon heterotopic transplantation differentiate neurons with phenotypic characteristics of their cortical site of origin (Pinaudeau et al., 2000, Eur. J. Neurosci., 12, 2486-2496).

Specific innervation of the rat thalamus by grafted noradrenergic locus coeruleus neurons.

Growth and distribution of noradrenaline (NA) fibres from the implant into the thalamus of host rats were examined at 5-13 months after the implantation by immunohistochemistry using NA or tyrosine hydroxylase antisera. Cell suspension dissociated from the locus coeruleus (LC) region of 14-day-old rat fetuses was implanted into the center of the unilateral thalamus in adult rats from which the noradrenergic afferents to the thalamus had been eliminated with 6-hydroxydopamine treatment. A dense network of varicose NA-immunoreactive (NA-IR) fibres extended laterally into the posterior thalamic nuclear group and the ventral posterolateral thalamic nucleus from the implant in a pattern similar to that the intrinsic noradrenergic fibres form in the normal thalamus, i.e. laterally rich and medially poor NA fibres. Electron microscopic observations revealed that varicosities of NA-IR fibres formed symmetrical as well as asymmetrical axodendritic synapses and axo-axonic synapses with the host neurons as seen in the normal thalamus. labelled dendrite-like fibres of graft origin penetrated deep into the host brain and received afferents from non-labelled axon terminals. Varicosities of NA-IR fibres in the LC implanted animal formed axo-dendritic synapses at the higher ratio than those in the normal animal did. These results show that implanted fetal noradrenergic neurons innervate target regions of the thalamus specifically as the noradrenergic fibres in the normal thalamus do and maintain the innervation for a long time in the noradrenergically denervated rats.

Motor function analysis of myelin mutant mice using a rotarod.

We have examined motor control in normal and shiverer mutant mice using the rotarod assay, a forced motor activity which tests for balance and co-ordination. Shiverer mice carry a deletion of the myelin basic protein (MBP) gene, resulting in CNS dysmyelination and characteristic motor dysfunction. Homozygous mutant mice had a significant increase in cumulative falls from the rotarod relative to heterozygous mice. Non-acclimated animals of both genotypes showed progressive improvement in performance when tested on successive days. The rotarod test also discriminated shiverer mutants from animals that received gene therapy intervention. Shiverer animals carrying an MBP transgene showed gene-dosage-dependent improvements in motor function, and mutants which received thalamic transplants of wild type oligodendrocyte precursor cells showed improvement relative to sham operated and non-transplanted controls. Thus the rotarod is a sensitive measure of motor function in hypomyelinated mice, and may be useful for assessing the results of experimental manipulations including transgenic gene therapy and cell transplantation.

The fate of human glial cells following transplantation in normal rodents and rodent models of neurodegenerative disease.

Investigations on xenografting in the brain have previously focused on the anatomical and functional integration of the transplanted neurons. More recently, astrocytes are being implicated as having complex functions following transplantation, and are being investigated to determine their role(s) in transplantation. The present study was undertaken to investigate the migration of human astrocytes following transplantation of thalamic, striatal, and mesencephalic tissue into the rodent striatum. Human donor fetuses (9-16 weeks in gestation) obtained through elective and spontaneous abortions were utilized in this study. Following transplantation, donor astrocytes were labeled with an antiserum directed against human glial fibrillary acidic protein. Our results demonstrate that astrocytic elements from all three tissue types are capable of incorporating into the host brain, and have a tendency to follow white matter tracts (such as the corpus callosum, internal capsule, and fiber bundles in the striatum). Human astrocytes, originating from the striatum and thalamus exhibited extensive migration, while migration was more limited in animals with ventral mesencephalon transplants. Ventral mesencephalon transplanted animal demonstrated positive astrocytes within the transplant, with processes (very few cell bodies) extending into white matter of adjacent host striatum. Astrocytes demonstrating immature morphology were observed with all transplant types, but were most prevalent in the striatal transplanted animals. The extent of astrocyte migration and the morphologies observed in this study reflect regional differences of the developing human brain. These results confirm and extend previous investigations on glial cell migration following transplantation in the brain.

Morphological maturation of thalamic neurons as studied in fetal neural transplants.

This study attempts to determine whether fetal thalamic neuroblasts from rat embryos (embryonic age 15 days) labeled with horseradish peroxidase (HRP) can differentiate into their normal dendritic phenotype when transplanted as a cell suspension into a lesioned site in the adult somatosensory thalamus. The HRP labeling provided a Golgi-like staining of numerous neurons up to 12-14 days after transplantation. There were three main results. 1) As early as 2 days after transplantation three morphologic cell types were observed: Two were bipolar and the third multipolar. These cellular profiles are characteristic of adult ventroposterolateral, reticular, and ventroposteromedial neurons and suggest that transplanted neurons can take shape in the absence of specific arrangements of afferent fibers. 2) The initial stage of dendritic growth was characterized by numerous growing specializations and consisted of a rapid, arborizing growth that appeared to proceed at an accelerated rate relative to normal development. During the later stage, which was characterized by the great reduction of growing specializations, dendritic remodeling resulted in a simpler morphology, and the transplanted neurons did not achieve an adult morphology. 3) Putative axons exhibiting growth cones were present in impressive densities in the transplants, and a number of them grew into the neuron-depleted host thalamus. A very small number of axons grew into host gray matter outside the lesioned area, indicating that neurodegenerative areas provide a better substrate for neurite outgrowth than intact tissue. In rare instances axons were visible in the internal capsule, indicating that the biochemical inhibition provided by mature myelin and oligodendrocytes may not be an absolute obstacle to axonal growth.

Tratamiento médico y quirúrgico de la enfermedad de Parkinson: estudio a largo plazo / Medical and surgical treatment of Parkinson's disease. A long term study

Este trabajo estudia los efectos del tratamiento médico y quirúrgico sobre el curso natural de la enfermedad de Parkinson. Tres grupos de pacientes fueron estudiados: I. Pacientes tratados con levodopa/carbidopa y anticolinérgicos (n = 10). II. Pacientes tratados con talamotomía (n = 9). III. Pacientes con tratamiento médico más trasplante autólogo de médula adrenal al núcleo caudado (n = 8). Fueron evaluados antes de iniciar el tratamiento médico o de efectuar la cirugía, al mes, a los seis meses y al año. Fueron usadas las escalas clínicas: New York Parkinson's Disease Scale, Unified Parkinson's Disease Scale, Schwab and England y Hoehn and Yarth Scale. Se evaluó por separado temblor, rigidez, bradicinesia y deterioro mental. Se uso un análisis de varianza tipo Friedman. Grupo I. No hubo mejoría significativa y sí un deterioro mental significativo al año. Grupo II. Hubo mejoría significativa del temblor y la rigidez, sin embargo el deterioro mental al año determinó un empeoramiento de la escala global. Grupo III. No hubo mejoría significativa, pero el deterioro al año fue menos pronunciado que para los otros grupos

Glutamic acid decarboxylase gene expression in thalamic reticular neurons transplanted as a cell suspension in the adult thalamus.

The goal of the present study was to determine whether alterations in neuronal morphology and connections in thalamic grafts were accompanied by changes in the expression of mRNA encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of GABA, the normal neurotransmitter of neurons of the thalamic reticular nucleus. Cell suspensions of rat fetal tissue containing both thalamic reticular nucleus and ventrobasal primordia were transplanted into the excitotoxically lesioned somatosensory thalamus of adult rats. Levels of messenger RNA (mRNA) encoding GAD (Mr 67,000; GAD67) were measured 7 days to 4 months following transplantation via quantitative in situ hybridization with 35S-radiolabeled antisense RNAs. Expression of GAD67 mRNA in the thalamic reticular nucleus was analyzed in parallel in rat pups between 0 and 30 days postnatally, and in adult animals. As already observed with immunohistochemistry, transplanted neurons of the thalamic reticular nucleus did not group in specific clusters but rather mingled with unlabeled (putatively ventrobasal) neurons. Levels of labelling for GAD67 mRNA per neuron increased over time and reached adult levels during the third week post-grafting, i.e. 2 weeks after the theoretical birthdate of the neurons (grafted at embryonic days 15-16). Similar values were observed and a plateau was reached at similar time points during normal ontogeny. The results suggest that, in contrast to morphology and size of the neuronal cell bodies, gene expression of GAD67 develops normally despite the ectopic location of neurons of the thalamic reticular nucleus in the somatosensory thalamus, the abnormal connectivity and the lack of segregation from non-GABAergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anatomic connections between homotopic transplant of fetal cortical tissue and optic thalamus in adult rats]. / Connessioni anatomiche tra trapianto omotopico di tessuto corticale fetale e talamo ottico di ratti adulti.

The present research was planned to study the possibility to reconstruct a damaged neural circuitry by replacing the injured neurons with homotopic fetal cells. In adult rats the motor cortex was injured with intracortical injection of kainic acid solution. After a delay of 10-14 days, a block of cerebral cortex of fetal rats (E17) was transplanted in the cavity produced by the kainic acid in the motor cortex. After 2-3 months, WGA-HRP solution was injected in the thalamus of the host and both anterogradely labeled fiber terminals and retrogradely labeled somata cells were researched in the transplanted cortex. The results showed that: 1) the host thalamus projects to the transplanted cortex with less density compared to the host cortex surrounding the transplant; 2) the thalamic projection to the transplant is not topographically organized whereas the projection to the host cortex is; 3) the transplant was virtually void of a significant projection to the thalamus of the host. In conclusion, the results offer direct evidence that the reconstruction of an injured thalamocortical circuitry of adult rat is not possible by transplanting homotopic fetal neurons.

Dissimilar responses of adult thalamic monoaminergic and somatosensory afferent fibers to implantation of thalamic fetal cells.

It is generally accepted that transplanted fetal neurons can, after several weeks to months, establish connections with the host CNS. Host afferent systems seem, however, to show different types of responses to the presence of grafted fetal neurons. The present study is a preliminary step to identify mechanisms involved in the reactions of adult axons to transplanted fetal neurons. The right ventrobasal thalamus of adult rats was depleted of neurons by in-situ injection of kainic acid and cell suspensions from homotopic thalamic embryonic primordia which were injected into the lesioned area. After various post-implantation delays, ranging from five to 30 days, two types of experiments were performed: (i) noradrenaline and serotonin immunohistochemistry with specific antibodies on alternate sections; and (ii) anterograde tracing using wheat germ agglutinin conjugated to horseradish peroxidase from the dorsal column nuclei and the principal sensory trigeminal nucleus. Five days after transplantation, host monoaminergic fibers (either noradrenergic or serotoninergic) had already grown into the transplants. Ingrowing fibers were thin and poorly varicose, exhibiting endings morphologically similar to the growth cones observed during axogenesis. Seven days after grafting, growth cones were no longer visible and monoaminergic fibers exhibited either normal-sized or very large varicosities. Large varicosities progressively decreased in number and, after three weeks, the fibers displayed a normal adult morphology, forming a dense network all over the transplants. In contrast, host somatosensory afferents, labeled by anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, did not grow into the transplants. Intermingling of somatosensory afferents and transplanted cells was observed only after 10 days, when grafted neurons extended outside the original transplantation site into the neuron-depleted area containing the somatosensory afferents. The present results demonstrate that adult monoaminergic and somatosensory afferents, when deprived of their usual target, do not react in a similar way to the addition of fetal neurons. It is proposed that adult monaminergic fibers have the ability to regain morphological (and probably functional) immature forms which were considered to be restricted to the period of axogenesis or to lesion-induced regeneration. In contrast, fetal transplants do not seem to induce, by themselves, a similar alteration of genetic expression in adult somatosensory neurons. It has been proposed that "diffuse" and "point-to-point" axonal systems may be differentiated in the CNS on anatomical bases. The present results add to the identification of two different systems by demonstrating that, in the thalamus, they present dissimilar responses to the implantation of fetal cells.

Vascularization of fetal cell suspension grafts in the excitotoxically lesioned adult rat thalamus.

Several studies have considered the establishment of vascularization in intracerebral solid transplants of neural tissue. The widely supported interpretation of the results is that the vascular network of the solid grafts is already present before implantation into the host brain. The situation is different when dissociated fetal tissue is transplanted as a cell suspension because in these conditions the fetal vascular network is disrupted. The present study has, therefore, been undertaken to follow the angiogenesis in a transplant of dissociated fetal cells implanted into the excitotoxically neuron-depleted thalamus. The vascular network is compared to that observed in the intact and in the lesioned thalamus both in terms of morphology of the capillaries and of the function of the blood-brain barrier (BBB). In the transplant, capillaries, stained by Indian ink, are very few in number and have very fine calibers during the first 20 days after grafting. Some structures can be identified as immature blood vessels at the electron microscopic level. The blood vessels are progressively more numerous in the graft and they demonstrate mature ultrastructural features 2 months after grafting. Last, there is no leakage of the BBB for peroxidase. The vascularization seems to follow a pattern of maturation comparable to that described during development in the literature. In contrast, in the lesioned area, there is a reactive angiogenesis: 10 days after the excitotoxic injection (shortest time studied), there are many wide caliber vessels with expanded perivascular spaces engorged with mesodermal cells. A microvascularization also develops transiently during the first two months. Capillaries are abnormal from the functional point of view, since there is a leakage of the BBB to macromolecules. The use of an experimental model in which transplant had to grow in a lesioned area permits to determine two types of vascularization: an apparently normal developmental timetable, normal morphological and functional characteristics, in the transplant; a reactive angiogenesis, in the lesioned area.

Regeneration of axons from the adult rat optic nerve: influence of fetal brain grafts, laminin, and artificial basement membrane.

After transection of the optic nerve of adult rats, most of the axons in the proximal stump die and the surviving ones are unable to regenerate into the distal optic nerve. Since the fetal brain has an inherent capacity to regenerate axons, we investigated whether fetal (E16) target regions of optic axons (thalamus and tectum) transplanted to the completely transected optic nerve of adult rats would promote axon regeneration. In control operated rats, axon growth beyond the site of transection was restricted to a few fibers that grew irregularly within the connective tissue scar. By contrast, in grafted animals directed outgrowth of optic axons toward the transplant started at 6 days postoperation (p.o.) and reached its maximum 15 days p.o. and later, when numerous single optic fibers and small axon fascicles had grown toward and into the graft, where they formed arborizations and terminal varicosities. Regenerating optic axons were further advanced than GFAP-positive strands of astroglia that emanated from the proximal optic nerve stump. Laminin immunoreactivity appeared at 6 days p.o. in the zone of reactive astroglia in the terminal part of the optic nerve stump. Later it showed a distribution complementary to the pattern of GFAP immunoreactivity, which it seemd to circumscribe. There was no unequivocal codistribution of laminin immunoreactivity with regenerating axons. In further experiments, target regions from different ontogenetic stages (E14 to neonate and adult) and nontarget regions (E16, cerebral cortex or spinal cord) were grafted to the optic nerve stump. With the exception of the adult grafts, all transplants had effects on axon regeneration comparable to those of E16 target regions. In order to test the effects of extracellular matrix molecules on axon regeneration, a basement membrane gel reconstituted from individual components of the Engelbreth-Holm-Sarcoma (EHS) sarcoma was implanted between proximal and distal optic nerve stumps. No axons were induced to regenerate by this matrix. Likewise, laminin adsorbed to nitrocellulose paper and implanted at the lesion site did not stimulate axon growth from the proximal optic nerve stump. These results indicate that fetal brain is able to induce and direct regrowth of axons from the optic nerve toward the graft across a substrate that is not composed of astroglia or basement membrane components like laminin. The directed growth of axons in the absence of a preformed substrate implies a chemotactic growth response along a concentration gradient mediated by neurotropic molecules released from the graft.

Somatic activation of thalamic neurons transplanted into lesioned somatosensory thalamus.

Homotypic fetal neurons were transplanted into previously lesioned ventrobasal complex of rats. After 1-3 months of survival the animals received injections of 2-deoxy-[14C]glucose to reveal metabolic activity of the transplanted cells in response to somatic stimuli. These experiments indicated that stimulus-evoked activity in the transplants of animals receiving a somatic stimulus was significantly greater than in the transplants of animals that were not stimulated. Control studies using cell counts, cytochrome oxidase and acetylcholinesterase histochemistry established that the differences in activity values were not due to the number of surviving cells or the metabolic health of the individual grafts.

Fetal medial habenula transplants: innervation of the rat interpeduncular nucleus.

The effects of donor age and site of placement on the survival of fetal medial habenula (MH) transplants into adult rats hosts were examined. The innervation of the interpeduncular nucleus (IPN) in such cases was also examined. Explants of MH consisting of the medial-dorsal lip of the third ventricle were held in vitro for 1-2 days. Colloidal gold conjugated to wheat germ agglutinin was added for the last 18 hours to label the cells. Four of 16 cases with E19 derived transplants contained donor neurons. Markedly larger transplants were present in 95% of 20 cases with E16 derived transplants. Sites in the ventral midbrain were successful, while limited or no survival occurred at sites more remote from IPN. Retrograde labeling of transplant neurons was present in each case studied with HRP injection into host IPN. Colloidal gold-labeled macrophages, some oriented capillaries and GFAP-positive processes marked the donor-host interface. In EM the interface was evident only by the difference in tissue elements in the transplant versus host. Numerous synapses of Gray types I and II were present in the transplant. Excellent survival of MH neurons, donor/host interfaces, innervation of IPN by the transplant and fine structure in and around the transplants, all suggest that such preparations are suitable for further experimental analysis of the habenulo-interpeduncular system.

First month of development of fetal neurons transplanted as a cell suspension into the adult CNS.

It has been demonstrated elsewhere that fetal thalamic tissue, when transplanted as a cell suspension into the excitotoxically neuron-depleted adult somatosensory thalamus, can grow, differentiate, and receive projections from host afferents. In the present study, we used the same paradigm to analyse the transplanted neurons during their morphogenesis, i.e. during the first month after transplantation. Using various anatomical criteria, at the light and electron microscope levels, we compared the development of transplanted neurons with the normal ontogeny of homologous neuronal populations. Confined solely to the mechanically lesioned area during implantation at seven days post-grafting, the transplant increased in size to occupy most of the previously neuron-depleted area by the third week after grafting. The final size of the transplant thus depended upon the size of the lesion. At seven days post-grafting, the neurons were small in size and the cellular density was high. At this immature stage few synaptic contacts were visible and the ultrastructure was characterized by large extracellular spaces. At 10 days post-grafting, the size of the neurons had increased and the cellular density had decreased. Both an extensive dendritic proliferation and a simultaneous active synaptogenesis could also be observed. All these events continued to evolve and during the third week the neuropil progressively acquired more mature ultrastructural characteristics. Synaptic contacts exhibiting characteristics comparable to those observed in the intact thalamus also became more numerous. At 20 days post-grafting, axonal myelination had started, the development of the graft apparently stopped and the various criteria had stabilized. Until that developmental stage, growth of grafted neurons compared to that of normal thalamic ones. At later stages, however, grafted neurons failed to grow larger and did not reach the size of the homologous population in the adult animal. It seems, therefore, that transplants of thalamic fetal neurons can be used as a tool with which to study thalamic neuronal development, within definable limits.

Rapid growth of host afferents into fetal thalamic transplants.

Fetal cell suspension grafts grow and differentiate when implanted into adult rat CNS areas previously neuron-depleted using an excitotoxin. There is some controversy in the literature concerning the timetable of establishment and possible extent of host-graft connections in these experimental conditions. The present study was undertaken to analyze the development of adult host monoaminergic afferents into a transplant formed by fetal thalamic neurons in the previously excitotoxically lesioned thalamus. It is demonstrated that both norepinephrin- and serotonin-immunoreactive fibers are present in the transplant as soon as 8 days after grafting. At those times, immunoreactive fibers exhibit morphological characteristics typically associated with immature stages. After longer survival time, up to 4 weeks after grafting, immunoreactive fibers are numerous in the transplant and exhibit morphological features comparable to those observed in the adult thalamus. These results demonstrate the rapid ingrowth of some fiber systems of the adult host into the transplant and suggest that grafted fetal cells can be functionally integrated into the host circuitry as soon as a few weeks after grafting.

Fetal homotypic transplant in the excitotoxically neuron-depleted thalamus: light microscopy.

One month after an in situ injection of kainic acid into the ventrobasal thalamic complex (VB), the lesioned area is totally depleted of neurons. The present study has been undertaken to determine the cytoarchitecture and connectivity of the nucleus constructed by fetal thalamic neurons implanted into the excitotoxically lesioned area. Adult rats received an injection of kainic acid inducing a total neuronal depletion of the right lateral thalamus (including both the nucleus reticularis thalami and the lateral portion of the ventrobasal complex). One month later, homotypic neurons were taken from the dorsal thalamic primordium of rat embryos (gestational age 15-16 days), dissociated, and injected into the lesioned area as a cell suspension. After 2-4-month survival, the cytoarchitecture of the neonucleus formed by the grafted neurons within the previously neuron-depleted area was analyzed. Additionally, connectivity was analyzed in seven rats in which dorsal column nuclei and/or cortical projections to the area were labeled anterogradely with either 3H-leucine or wheat-germ agglutinin conjugated to HRP, and the animals were perfused and processed following various histological procedures (Nissl staining, autoradiographic processing, and histochemistry for visualization of peroxidase). Fetal neurons grew, differentiated, and progressively occupied the previously neuron-depleted area of the adult host CNS. They organized themselves into a neonucleus with particular cytoarchitectural features including 1) the existence of two concentric zones--a central zone containing neurons and glial cells and a marginal zone only filled with a band of glial cells, 2) an increase in cellular density compared to the intact thalamus, 3) the grouping of neurons in spherical clusters, and 4) apparent polymorphism of neuronal somata. Lemniscal and corticothalamic afferents originating from the host were observed in the neonucleus when the fetal neurons had been implanted correctly into the lesioned area but not when they had been misplaced into either normal thalamic tissue or the internal capsule. The afferents labeled from either the dorsal column nuclei or the somatosensory cortex were, however, less dense in the neonucleus than in the normal thalamus. These results are discussed with regard to the normal cytoarchitecture and connectivity of the ventrobasal complex of the rat thalamus.