Target-specific innervation of embryonic cerebellar transplants by regenerating olivocerebellar axons in the adult rat.
The reestablishment of topographically organized connections is a necessary prerequisite to obtain a full anatomical repair following brain injury. One system where such an issue can be addressed is the olivocerebellar system, where, normally, clusters of inferior olive neurons project to neurochemically heterogeneous Purkinje cell compartments defined by the expression of cell-specific markers, such as zebrin II. To assess whether adult injured olivocerebellar axons that regenerate into cerebellar transplants are able to establish target-specific innervation of grafted Purkinje cells, we made surgical transections in the white matter of adult rat cerebella and placed solid grafts from the embryonic cerebellar anlage into the lesion site. The transplanted tissue developed highly organized minicerebella, in which Purkinje cells were distributed into distinct clusters of zebrin II-immunopositive or -immunonegative neurons, mimicking the cortical compartments present in the normal adult cerebellum. Olivocerebellar axons, labeled by biotinylated dextran amine tracing, regenerated into the transplants where they formed discrete patches made of several terminal arbors impinging upon Purkinje cell dendrites. Among 401 such climbing fiber patches, 96% exclusively innervated Purkinje cells of either phenotype and stopped at the border of the zebrin II(+/-) Purkinje cell clusters, whereas only 4% were extended across this boundary and innervated both zebrin II-positive and -negative Purkinje cells. The results obtained support the view that the embryonic cerebellar tissue provides target-specific information that can be decoded by ingrowing adult olivocerebellar axons in order to establish appropriate innervation patterns with zebrin II-positive or -negative Purkinje cell compartments.
Rossi
Ferdinando
F
Rita Levi Montalcini Centre for Brain Repair, Department of Neuroscience, University of Turin, Turin, Italy.
Saggiorato
Claudia
C
Strata
Piergiorgio
P
D000818:Animals; D001369:Axons / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives*; D016380:Brain Tissue Transplantation; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D003911:Dextrans; D016332:Fetal Tissue Transplantation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009434:Neural Pathways / Q000166:cytology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D009847:Olivary Nucleus / Q000166:cytology* / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*
D003911:Dextrans; D009419:Nerve Tissue Proteins; C076397:biotinylated dextran amine; C071871:zebrin II; D001710:Biotin