Differentiation of cerebellar anlage heterotopically transplanted to adult rat brain: a light and electron microscopic study.
Pieces of cerebellar primordia from (days 14 or 15 of gestation) E14 or E15 rat embryos were dissected out and transplanted into a cavity of the occipital cortex and underlying hippocampus, over the superior colliculus of 2-month-old rats. The host animals were allowed to survive for 2 to 3 months. The cytoarchitectonic and the synaptic organizations were analyzed in 16 of such transplants. Only 4 of the implants established connections with the host brain through several thin peduncles composed of myelinated fibers. The remaining 12 implants survived in an extraparenchymal situation. Independently of its partial linking to the host brain, the graft grew and developed a cerebellar structure composed of nuclear and cortical regions. The latter exhibited normal lamination and foliation, and contained the five categories of neurons which characterize normal cerebellar cortex. Electron microscopic examination disclosed that the synaptic connections normally present in the cerebellar cortex were also formed in the implants with the exception of climbing fibers, which were absent. The cerebellar interneurons kept their normal topographic distribution and gave origin to numerous synapses which maintained their own specificity. Some mossy fibers were present in the granule cell layer at the center of typical glomeruli. However, abnormal synaptic arrangements were also observed within the neuropil of this granule cell layer. They consisted of pseudoglomerular formations composed of clusters of tightly packed small axon terminals covered by granule cell dendrites. The origin of these boutons was not established. Since they did not correspond to the classes of presynaptic elements normally synapsing on these dendrites, they constitute a new example of cerebellar heterologous synapses. Their presence could be related to changes in the cellular environment due to the rarity of mossy afferents. HRP tracing experiments, carried out in extraparenchymal transplants, have allowed us to determine that the corticonucleocortical loop of normal cerebellum is also developed in the implants. Nuclear neurons are at the origin of the mossy fibers involved in glomerular formations, whereas Purkinje cells project to the nuclear region. The establishment of these reciprocal connections could determine the functional stabilization of both kinds of cerebellar neurons and thus the long survival of extraparenchymal grafts. These results allow the conclusion that the presence of extracerebellar afferents is not necessary for the organotypic and synaptotypic differentiation of cerebellar anlage.
D000818:Animals; D002454:Cell Differentiation; D002531:Cerebellum / Q000166:cytology / Q000196:embryology* / Q000637:transplantation; D005260:Female; D007395:Interneurons / Q000166:cytology; D008854:Microscopy, Electron; D009928:Organ Specificity; D011689:Purkinje Cells / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000648:ultrastructure